/ en Wed, 21 May 25 17:00:58 -0400 /news/genomic-score-predicts-patients-progression-multiple-myeloma <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" class="datetime">May 21, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Mutation-based score provides a personalized indicator of disease severity and progression risk, could help inform early intervention strategies</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Elizabeth Dougherty, Dana-Farber Cancer Institute </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" title="Wednesday, May 21, 2025 - 17:00" class="datetime">May 21, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=Vs6PpQYV 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=dWM9v_mQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=8rAVs0u_ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S" alt="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," title="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Multiple myeloma tumor cells (green) </div> </div> </article> </div> </div> </div> </div> </div> </div> <div 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href="/cancer">Cancer Program</a></div> <div class="field__item"><a href="/cancer/cancer-genome-computational-analysis">Cancer Genome Computational Analysis</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-use-genetics-dig-tumors-past" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a 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field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/mathematical-model-finds-cancer-mutations-matter"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source 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/> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/mathematical-model-finds-cancer-mutations-matter" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Mathematical model finds the cancer mutations that matter</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>A new risk assessment score developed by researchers at Dana-Farber Cancer Institute, the ӳ����ý of MIT and Harvard, and Massachusetts General Hospital reveals how multiple myeloma, a form of blood cancer, begins and progresses from precancerous to malignant states by tracing DNA mutations. The score, called an MM-like score, assesses the severity of disease and risk of progression to active cancer, with higher scores indicating faster progression. In the future, the MM-like score could be used in clinical practice to inform decisions about early intervention. </p> <p>“In patients with a precursor condition for multiple myeloma, the multiple myeloma-like score helps to predict who is at a higher risk of progressing to active cancer,” said co-senior author Jean-Baptiste Alberge, an instructor in medicine at Dana-Farber and postdoctoral scholar at the ӳ����ý. “This study brings us closer to more personalized care for patients with a precursor stage of cancer and could better inform early intervention strategies in the future.”</p> <p>The study was published in <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank"><em>Nature Genetics</em></a>.</p> <p>Multiple myeloma is a cancer in plasma cells that affects 32,000 individuals in the United States each year. Prior to developing multiple myeloma, patients go through precursor stages of the disease called monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). Approximately 1 to 10 percent of patients with these conditions progress to active multiple myeloma per year, with 50-percent of high-risk SMM cases progressing within two years.</p> <p>“There has been an urgent need to identify genomic risk factors that predict disease progression in smoldering myeloma,” said Irene Ghobrial, director of the Center for Early Detection and Interception of Blood Cancers at Dana-Farber and an associate member of the ӳ����ý. “This is especially true as we start early therapeutic interception for high risk SMM. Our data provides a simple genomic score that can help predict progression and can improve on our clinical markers to help stratify risk for our patients.” </p> <p>Existing risk stratification models for multiple myeloma characterize patients as “high” or “low” risk based on measures of tumor burden. These models do not include genetic factors. The MM-like score defined in this study focuses on the presence and progressive evolution of genetic abnormalities to assess the state of the disease. The MM-like score increases over time with the accumulation of mutations that drive the disease. </p> <p>“Treating risk as simply ‘high’ or ‘low’ fails to capture the complexity of tumor timing and evolution, and we saw an opportunity to redefine it through whole-genome sequencing,” said Alberge.</p> <p>Along with co-first authors Ankit Dutta, a postdoctoral fellow in the Ghobrial lab; Andrea Poletti, a post-doctoral fellow at the University of Bologna, Italy; and collaborators from the UK, Germany, and Greece, Alberge compiled mostly whole genome sequencing data from over 1,000 individuals with multiple myeloma and precursor conditions, including 218 patients with MGUS or SMM. The study provides one of the largest analyses of whole genome data for multiple myeloma and its precursor conditions to date.</p> <p>"This study greatly improves our ability to discover both potentially clinically-actionable cancer-driving mutations in MM and the timing of when these events occur across disease states," said <a href="/node/4864">Gad Getz</a>, a core institute member of the ӳ����ý, director of the <a href="/node/45711">Cancer Genome Computational Analysis</a> group in the ӳ����ý’s <a href="/node/8529">Cancer Program</a>, and director of bioinformatics in the Krantz Family Center for Cancer Research and the Department of Pathology at Massachusetts General Hospital. "These insights wouldn't be possible without access to deeply sequenced whole genomes from a large number of patients and across different disease stages."</p> <p>By comparing mutations that were more commonly found in active disease than in asymptomatic precursor forms, they were able to identify genes that are likely linked to the transformation to active disease. The study also revealed the likely order and timing of genetic mutations.</p> <p>To validate the score, the team evaluated 47 tumor samples from 20 patients at various points in the progression of disease. They found that the MM-like scores in individual patients reflected the course of their disease in multiple cases. For example, 11 of 13 patients who did not progress during the period of observation had stable MM-like scores, and 5 of 7 patients who did progress had MM-scores that increased at the time of progression.</p> <p>The study also uncovered surprising findings about the origins of multiple myeloma. The team estimates based on this study that the earliest genomic changes related to the disease may appear very early in life, in the patient’s 20s or 30s, even though multiple myeloma is typically not diagnosed until much later. </p> <p>To make the MM-like score more clinically accessible, the team is developing a test based on liquid biopsies instead of bone marrow biopsies to collect DNA. This change would potentially enable more frequent monitoring of the evolution of the condition. In addition, the team aims to continue to validate and improve the score by studying more patients over longer periods of time.</p> <p><em>Adapted from <a href="https://www.dana-farber.org/newsroom/news-releases/2025/dana-farber-genomic-score-predicts-progression-to-multiple-myeloma" target="_blank">a press release</a> issued by Dana-Farber Cancer Institute.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the Multiple Myeloma Research Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the International Myeloma Society, Dana-Farber Cancer Institute, the Krouse Family Foundation, the National Cancer Institute, and Stand Up to Cancer. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Alberge J-B, Dutta AK, Poletti A, et al. <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank">Genomic landscape of multiple myeloma and its precursor conditions</a>. <em>Nature Genetics</em>. Online May 21, 2025. DOI: 10.1038/s41588-025-02196-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Wed, 21 May 2025 21:00:58 +0000 tulrich@broadinstitute.org 5558731 at /news/six-scientists-named-new-core-institute-members-broad <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" class="datetime">May 21, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Mutation-based score provides a personalized indicator of disease severity and progression risk, could help inform early intervention strategies</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Elizabeth Dougherty, Dana-Farber Cancer Institute </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" title="Wednesday, May 21, 2025 - 17:00" class="datetime">May 21, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=Vs6PpQYV 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=dWM9v_mQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=8rAVs0u_ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S" alt="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," title="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Multiple myeloma tumor cells (green) </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link 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Computational Analysis</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-use-genetics-dig-tumors-past" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/scientists-use-genetics-dig-tumors-past"><picture> <source 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field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/mathematical-model-finds-cancer-mutations-matter"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=EJBMeaUB 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0" alt="Credit: Susanna Hamilton" title="Credit: Susanna Hamilton" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/mathematical-model-finds-cancer-mutations-matter" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Mathematical model finds the cancer mutations that matter</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>A new risk assessment score developed by researchers at Dana-Farber Cancer Institute, the ӳ����ý of MIT and Harvard, and Massachusetts General Hospital reveals how multiple myeloma, a form of blood cancer, begins and progresses from precancerous to malignant states by tracing DNA mutations. The score, called an MM-like score, assesses the severity of disease and risk of progression to active cancer, with higher scores indicating faster progression. In the future, the MM-like score could be used in clinical practice to inform decisions about early intervention. </p> <p>“In patients with a precursor condition for multiple myeloma, the multiple myeloma-like score helps to predict who is at a higher risk of progressing to active cancer,” said co-senior author Jean-Baptiste Alberge, an instructor in medicine at Dana-Farber and postdoctoral scholar at the ӳ����ý. “This study brings us closer to more personalized care for patients with a precursor stage of cancer and could better inform early intervention strategies in the future.”</p> <p>The study was published in <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank"><em>Nature Genetics</em></a>.</p> <p>Multiple myeloma is a cancer in plasma cells that affects 32,000 individuals in the United States each year. Prior to developing multiple myeloma, patients go through precursor stages of the disease called monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). Approximately 1 to 10 percent of patients with these conditions progress to active multiple myeloma per year, with 50-percent of high-risk SMM cases progressing within two years.</p> <p>“There has been an urgent need to identify genomic risk factors that predict disease progression in smoldering myeloma,” said Irene Ghobrial, director of the Center for Early Detection and Interception of Blood Cancers at Dana-Farber and an associate member of the ӳ����ý. “This is especially true as we start early therapeutic interception for high risk SMM. Our data provides a simple genomic score that can help predict progression and can improve on our clinical markers to help stratify risk for our patients.” </p> <p>Existing risk stratification models for multiple myeloma characterize patients as “high” or “low” risk based on measures of tumor burden. These models do not include genetic factors. The MM-like score defined in this study focuses on the presence and progressive evolution of genetic abnormalities to assess the state of the disease. The MM-like score increases over time with the accumulation of mutations that drive the disease. </p> <p>“Treating risk as simply ‘high’ or ‘low’ fails to capture the complexity of tumor timing and evolution, and we saw an opportunity to redefine it through whole-genome sequencing,” said Alberge.</p> <p>Along with co-first authors Ankit Dutta, a postdoctoral fellow in the Ghobrial lab; Andrea Poletti, a post-doctoral fellow at the University of Bologna, Italy; and collaborators from the UK, Germany, and Greece, Alberge compiled mostly whole genome sequencing data from over 1,000 individuals with multiple myeloma and precursor conditions, including 218 patients with MGUS or SMM. The study provides one of the largest analyses of whole genome data for multiple myeloma and its precursor conditions to date.</p> <p>"This study greatly improves our ability to discover both potentially clinically-actionable cancer-driving mutations in MM and the timing of when these events occur across disease states," said <a href="/node/4864">Gad Getz</a>, a core institute member of the ӳ����ý, director of the <a href="/node/45711">Cancer Genome Computational Analysis</a> group in the ӳ����ý’s <a href="/node/8529">Cancer Program</a>, and director of bioinformatics in the Krantz Family Center for Cancer Research and the Department of Pathology at Massachusetts General Hospital. "These insights wouldn't be possible without access to deeply sequenced whole genomes from a large number of patients and across different disease stages."</p> <p>By comparing mutations that were more commonly found in active disease than in asymptomatic precursor forms, they were able to identify genes that are likely linked to the transformation to active disease. The study also revealed the likely order and timing of genetic mutations.</p> <p>To validate the score, the team evaluated 47 tumor samples from 20 patients at various points in the progression of disease. They found that the MM-like scores in individual patients reflected the course of their disease in multiple cases. For example, 11 of 13 patients who did not progress during the period of observation had stable MM-like scores, and 5 of 7 patients who did progress had MM-scores that increased at the time of progression.</p> <p>The study also uncovered surprising findings about the origins of multiple myeloma. The team estimates based on this study that the earliest genomic changes related to the disease may appear very early in life, in the patient’s 20s or 30s, even though multiple myeloma is typically not diagnosed until much later. </p> <p>To make the MM-like score more clinically accessible, the team is developing a test based on liquid biopsies instead of bone marrow biopsies to collect DNA. This change would potentially enable more frequent monitoring of the evolution of the condition. In addition, the team aims to continue to validate and improve the score by studying more patients over longer periods of time.</p> <p><em>Adapted from <a href="https://www.dana-farber.org/newsroom/news-releases/2025/dana-farber-genomic-score-predicts-progression-to-multiple-myeloma" target="_blank">a press release</a> issued by Dana-Farber Cancer Institute.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the Multiple Myeloma Research Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the International Myeloma Society, Dana-Farber Cancer Institute, the Krouse Family Foundation, the National Cancer Institute, and Stand Up to Cancer. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Alberge J-B, Dutta AK, Poletti A, et al. <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank">Genomic landscape of multiple myeloma and its precursor conditions</a>. <em>Nature Genetics</em>. Online May 21, 2025. DOI: 10.1038/s41588-025-02196-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Wed, 07 Aug 2024 12:56:43 +0000 Corie Lok 5557161 at /news/three-studies-highlight-how-proteins-are-altered-multiple-cancer-types <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" class="datetime">May 21, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Mutation-based score provides a personalized indicator of disease severity and progression risk, could help inform early intervention strategies</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Elizabeth Dougherty, Dana-Farber Cancer Institute </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" title="Wednesday, May 21, 2025 - 17:00" class="datetime">May 21, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=Vs6PpQYV 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=dWM9v_mQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=8rAVs0u_ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S" alt="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," title="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Multiple myeloma tumor cells (green) </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link 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Computational Analysis</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-use-genetics-dig-tumors-past" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/scientists-use-genetics-dig-tumors-past"><picture> <source 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field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/mathematical-model-finds-cancer-mutations-matter"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=EJBMeaUB 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0" alt="Credit: Susanna Hamilton" title="Credit: Susanna Hamilton" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/mathematical-model-finds-cancer-mutations-matter" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Mathematical model finds the cancer mutations that matter</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>A new risk assessment score developed by researchers at Dana-Farber Cancer Institute, the ӳ����ý of MIT and Harvard, and Massachusetts General Hospital reveals how multiple myeloma, a form of blood cancer, begins and progresses from precancerous to malignant states by tracing DNA mutations. The score, called an MM-like score, assesses the severity of disease and risk of progression to active cancer, with higher scores indicating faster progression. In the future, the MM-like score could be used in clinical practice to inform decisions about early intervention. </p> <p>“In patients with a precursor condition for multiple myeloma, the multiple myeloma-like score helps to predict who is at a higher risk of progressing to active cancer,” said co-senior author Jean-Baptiste Alberge, an instructor in medicine at Dana-Farber and postdoctoral scholar at the ӳ����ý. “This study brings us closer to more personalized care for patients with a precursor stage of cancer and could better inform early intervention strategies in the future.”</p> <p>The study was published in <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank"><em>Nature Genetics</em></a>.</p> <p>Multiple myeloma is a cancer in plasma cells that affects 32,000 individuals in the United States each year. Prior to developing multiple myeloma, patients go through precursor stages of the disease called monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). Approximately 1 to 10 percent of patients with these conditions progress to active multiple myeloma per year, with 50-percent of high-risk SMM cases progressing within two years.</p> <p>“There has been an urgent need to identify genomic risk factors that predict disease progression in smoldering myeloma,” said Irene Ghobrial, director of the Center for Early Detection and Interception of Blood Cancers at Dana-Farber and an associate member of the ӳ����ý. “This is especially true as we start early therapeutic interception for high risk SMM. Our data provides a simple genomic score that can help predict progression and can improve on our clinical markers to help stratify risk for our patients.” </p> <p>Existing risk stratification models for multiple myeloma characterize patients as “high” or “low” risk based on measures of tumor burden. These models do not include genetic factors. The MM-like score defined in this study focuses on the presence and progressive evolution of genetic abnormalities to assess the state of the disease. The MM-like score increases over time with the accumulation of mutations that drive the disease. </p> <p>“Treating risk as simply ‘high’ or ‘low’ fails to capture the complexity of tumor timing and evolution, and we saw an opportunity to redefine it through whole-genome sequencing,” said Alberge.</p> <p>Along with co-first authors Ankit Dutta, a postdoctoral fellow in the Ghobrial lab; Andrea Poletti, a post-doctoral fellow at the University of Bologna, Italy; and collaborators from the UK, Germany, and Greece, Alberge compiled mostly whole genome sequencing data from over 1,000 individuals with multiple myeloma and precursor conditions, including 218 patients with MGUS or SMM. The study provides one of the largest analyses of whole genome data for multiple myeloma and its precursor conditions to date.</p> <p>"This study greatly improves our ability to discover both potentially clinically-actionable cancer-driving mutations in MM and the timing of when these events occur across disease states," said <a href="/node/4864">Gad Getz</a>, a core institute member of the ӳ����ý, director of the <a href="/node/45711">Cancer Genome Computational Analysis</a> group in the ӳ����ý’s <a href="/node/8529">Cancer Program</a>, and director of bioinformatics in the Krantz Family Center for Cancer Research and the Department of Pathology at Massachusetts General Hospital. "These insights wouldn't be possible without access to deeply sequenced whole genomes from a large number of patients and across different disease stages."</p> <p>By comparing mutations that were more commonly found in active disease than in asymptomatic precursor forms, they were able to identify genes that are likely linked to the transformation to active disease. The study also revealed the likely order and timing of genetic mutations.</p> <p>To validate the score, the team evaluated 47 tumor samples from 20 patients at various points in the progression of disease. They found that the MM-like scores in individual patients reflected the course of their disease in multiple cases. For example, 11 of 13 patients who did not progress during the period of observation had stable MM-like scores, and 5 of 7 patients who did progress had MM-scores that increased at the time of progression.</p> <p>The study also uncovered surprising findings about the origins of multiple myeloma. The team estimates based on this study that the earliest genomic changes related to the disease may appear very early in life, in the patient’s 20s or 30s, even though multiple myeloma is typically not diagnosed until much later. </p> <p>To make the MM-like score more clinically accessible, the team is developing a test based on liquid biopsies instead of bone marrow biopsies to collect DNA. This change would potentially enable more frequent monitoring of the evolution of the condition. In addition, the team aims to continue to validate and improve the score by studying more patients over longer periods of time.</p> <p><em>Adapted from <a href="https://www.dana-farber.org/newsroom/news-releases/2025/dana-farber-genomic-score-predicts-progression-to-multiple-myeloma" target="_blank">a press release</a> issued by Dana-Farber Cancer Institute.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the Multiple Myeloma Research Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the International Myeloma Society, Dana-Farber Cancer Institute, the Krouse Family Foundation, the National Cancer Institute, and Stand Up to Cancer. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Alberge J-B, Dutta AK, Poletti A, et al. <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank">Genomic landscape of multiple myeloma and its precursor conditions</a>. <em>Nature Genetics</em>. Online May 21, 2025. DOI: 10.1038/s41588-025-02196-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Mon, 14 Aug 2023 15:00:00 +0000 adicorat 1282621 at /news/scientists-use-genetics-dig-tumors-past <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" class="datetime">May 21, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Mutation-based score provides a personalized indicator of disease severity and progression risk, could help inform early intervention strategies</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Elizabeth Dougherty, Dana-Farber Cancer Institute </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" title="Wednesday, May 21, 2025 - 17:00" class="datetime">May 21, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=Vs6PpQYV 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=dWM9v_mQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=8rAVs0u_ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S" alt="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," title="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Multiple myeloma tumor cells (green) </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" 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Computational Analysis</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-use-genetics-dig-tumors-past" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/scientists-use-genetics-dig-tumors-past"><picture> <source 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field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/mathematical-model-finds-cancer-mutations-matter"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=EJBMeaUB 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0" alt="Credit: Susanna Hamilton" title="Credit: Susanna Hamilton" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/mathematical-model-finds-cancer-mutations-matter" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Mathematical model finds the cancer mutations that matter</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>A new risk assessment score developed by researchers at Dana-Farber Cancer Institute, the ӳ����ý of MIT and Harvard, and Massachusetts General Hospital reveals how multiple myeloma, a form of blood cancer, begins and progresses from precancerous to malignant states by tracing DNA mutations. The score, called an MM-like score, assesses the severity of disease and risk of progression to active cancer, with higher scores indicating faster progression. In the future, the MM-like score could be used in clinical practice to inform decisions about early intervention. </p> <p>“In patients with a precursor condition for multiple myeloma, the multiple myeloma-like score helps to predict who is at a higher risk of progressing to active cancer,” said co-senior author Jean-Baptiste Alberge, an instructor in medicine at Dana-Farber and postdoctoral scholar at the ӳ����ý. “This study brings us closer to more personalized care for patients with a precursor stage of cancer and could better inform early intervention strategies in the future.”</p> <p>The study was published in <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank"><em>Nature Genetics</em></a>.</p> <p>Multiple myeloma is a cancer in plasma cells that affects 32,000 individuals in the United States each year. Prior to developing multiple myeloma, patients go through precursor stages of the disease called monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). Approximately 1 to 10 percent of patients with these conditions progress to active multiple myeloma per year, with 50-percent of high-risk SMM cases progressing within two years.</p> <p>“There has been an urgent need to identify genomic risk factors that predict disease progression in smoldering myeloma,” said Irene Ghobrial, director of the Center for Early Detection and Interception of Blood Cancers at Dana-Farber and an associate member of the ӳ����ý. “This is especially true as we start early therapeutic interception for high risk SMM. Our data provides a simple genomic score that can help predict progression and can improve on our clinical markers to help stratify risk for our patients.” </p> <p>Existing risk stratification models for multiple myeloma characterize patients as “high” or “low” risk based on measures of tumor burden. These models do not include genetic factors. The MM-like score defined in this study focuses on the presence and progressive evolution of genetic abnormalities to assess the state of the disease. The MM-like score increases over time with the accumulation of mutations that drive the disease. </p> <p>“Treating risk as simply ‘high’ or ‘low’ fails to capture the complexity of tumor timing and evolution, and we saw an opportunity to redefine it through whole-genome sequencing,” said Alberge.</p> <p>Along with co-first authors Ankit Dutta, a postdoctoral fellow in the Ghobrial lab; Andrea Poletti, a post-doctoral fellow at the University of Bologna, Italy; and collaborators from the UK, Germany, and Greece, Alberge compiled mostly whole genome sequencing data from over 1,000 individuals with multiple myeloma and precursor conditions, including 218 patients with MGUS or SMM. The study provides one of the largest analyses of whole genome data for multiple myeloma and its precursor conditions to date.</p> <p>"This study greatly improves our ability to discover both potentially clinically-actionable cancer-driving mutations in MM and the timing of when these events occur across disease states," said <a href="/node/4864">Gad Getz</a>, a core institute member of the ӳ����ý, director of the <a href="/node/45711">Cancer Genome Computational Analysis</a> group in the ӳ����ý’s <a href="/node/8529">Cancer Program</a>, and director of bioinformatics in the Krantz Family Center for Cancer Research and the Department of Pathology at Massachusetts General Hospital. "These insights wouldn't be possible without access to deeply sequenced whole genomes from a large number of patients and across different disease stages."</p> <p>By comparing mutations that were more commonly found in active disease than in asymptomatic precursor forms, they were able to identify genes that are likely linked to the transformation to active disease. The study also revealed the likely order and timing of genetic mutations.</p> <p>To validate the score, the team evaluated 47 tumor samples from 20 patients at various points in the progression of disease. They found that the MM-like scores in individual patients reflected the course of their disease in multiple cases. For example, 11 of 13 patients who did not progress during the period of observation had stable MM-like scores, and 5 of 7 patients who did progress had MM-scores that increased at the time of progression.</p> <p>The study also uncovered surprising findings about the origins of multiple myeloma. The team estimates based on this study that the earliest genomic changes related to the disease may appear very early in life, in the patient’s 20s or 30s, even though multiple myeloma is typically not diagnosed until much later. </p> <p>To make the MM-like score more clinically accessible, the team is developing a test based on liquid biopsies instead of bone marrow biopsies to collect DNA. This change would potentially enable more frequent monitoring of the evolution of the condition. In addition, the team aims to continue to validate and improve the score by studying more patients over longer periods of time.</p> <p><em>Adapted from <a href="https://www.dana-farber.org/newsroom/news-releases/2025/dana-farber-genomic-score-predicts-progression-to-multiple-myeloma" target="_blank">a press release</a> issued by Dana-Farber Cancer Institute.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the Multiple Myeloma Research Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the International Myeloma Society, Dana-Farber Cancer Institute, the Krouse Family Foundation, the National Cancer Institute, and Stand Up to Cancer. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Alberge J-B, Dutta AK, Poletti A, et al. <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank">Genomic landscape of multiple myeloma and its precursor conditions</a>. <em>Nature Genetics</em>. Online May 21, 2025. DOI: 10.1038/s41588-025-02196-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Thu, 20 Apr 2023 15:05:38 +0000 tulrich@broadinstitute.org 1282126 at /news/lung-cancers-molecular-features-shed-light-immunotherapy-response <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" class="datetime">May 21, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Mutation-based score provides a personalized indicator of disease severity and progression risk, could help inform early intervention strategies</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Elizabeth Dougherty, Dana-Farber Cancer Institute </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" title="Wednesday, May 21, 2025 - 17:00" class="datetime">May 21, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=Vs6PpQYV 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=dWM9v_mQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=8rAVs0u_ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S" alt="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," title="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Multiple myeloma tumor cells (green) </div> </div> </article> </div> </div> </div> </div> </div> </div> <div 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class="field__item"><article about="/news/immune-system-changes-occur-early-development-multiple-myeloma" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/immune-system-changes-occur-early-development-multiple-myeloma"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=BczEf_qo 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=BczEf_qo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=znO9iHCY 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=znO9iHCY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=vpGL-26K 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=J19UOuqg 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=J19UOuqg" alt="Lauren Solomon, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/immune-system-changes-occur-early-development-multiple-myeloma" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Immune system changes occur early in development of multiple myeloma</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/mathematical-model-finds-cancer-mutations-matter" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/mathematical-model-finds-cancer-mutations-matter"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=EJBMeaUB 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0" alt="Credit: Susanna Hamilton" title="Credit: Susanna Hamilton" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/mathematical-model-finds-cancer-mutations-matter" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Mathematical model finds the cancer mutations that matter</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>A new risk assessment score developed by researchers at Dana-Farber Cancer Institute, the ӳ����ý of MIT and Harvard, and Massachusetts General Hospital reveals how multiple myeloma, a form of blood cancer, begins and progresses from precancerous to malignant states by tracing DNA mutations. The score, called an MM-like score, assesses the severity of disease and risk of progression to active cancer, with higher scores indicating faster progression. In the future, the MM-like score could be used in clinical practice to inform decisions about early intervention. </p> <p>“In patients with a precursor condition for multiple myeloma, the multiple myeloma-like score helps to predict who is at a higher risk of progressing to active cancer,” said co-senior author Jean-Baptiste Alberge, an instructor in medicine at Dana-Farber and postdoctoral scholar at the ӳ����ý. “This study brings us closer to more personalized care for patients with a precursor stage of cancer and could better inform early intervention strategies in the future.”</p> <p>The study was published in <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank"><em>Nature Genetics</em></a>.</p> <p>Multiple myeloma is a cancer in plasma cells that affects 32,000 individuals in the United States each year. Prior to developing multiple myeloma, patients go through precursor stages of the disease called monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). Approximately 1 to 10 percent of patients with these conditions progress to active multiple myeloma per year, with 50-percent of high-risk SMM cases progressing within two years.</p> <p>“There has been an urgent need to identify genomic risk factors that predict disease progression in smoldering myeloma,” said Irene Ghobrial, director of the Center for Early Detection and Interception of Blood Cancers at Dana-Farber and an associate member of the ӳ����ý. “This is especially true as we start early therapeutic interception for high risk SMM. Our data provides a simple genomic score that can help predict progression and can improve on our clinical markers to help stratify risk for our patients.” </p> <p>Existing risk stratification models for multiple myeloma characterize patients as “high” or “low” risk based on measures of tumor burden. These models do not include genetic factors. The MM-like score defined in this study focuses on the presence and progressive evolution of genetic abnormalities to assess the state of the disease. The MM-like score increases over time with the accumulation of mutations that drive the disease. </p> <p>“Treating risk as simply ‘high’ or ‘low’ fails to capture the complexity of tumor timing and evolution, and we saw an opportunity to redefine it through whole-genome sequencing,” said Alberge.</p> <p>Along with co-first authors Ankit Dutta, a postdoctoral fellow in the Ghobrial lab; Andrea Poletti, a post-doctoral fellow at the University of Bologna, Italy; and collaborators from the UK, Germany, and Greece, Alberge compiled mostly whole genome sequencing data from over 1,000 individuals with multiple myeloma and precursor conditions, including 218 patients with MGUS or SMM. The study provides one of the largest analyses of whole genome data for multiple myeloma and its precursor conditions to date.</p> <p>"This study greatly improves our ability to discover both potentially clinically-actionable cancer-driving mutations in MM and the timing of when these events occur across disease states," said <a href="/node/4864">Gad Getz</a>, a core institute member of the ӳ����ý, director of the <a href="/node/45711">Cancer Genome Computational Analysis</a> group in the ӳ����ý’s <a href="/node/8529">Cancer Program</a>, and director of bioinformatics in the Krantz Family Center for Cancer Research and the Department of Pathology at Massachusetts General Hospital. "These insights wouldn't be possible without access to deeply sequenced whole genomes from a large number of patients and across different disease stages."</p> <p>By comparing mutations that were more commonly found in active disease than in asymptomatic precursor forms, they were able to identify genes that are likely linked to the transformation to active disease. The study also revealed the likely order and timing of genetic mutations.</p> <p>To validate the score, the team evaluated 47 tumor samples from 20 patients at various points in the progression of disease. They found that the MM-like scores in individual patients reflected the course of their disease in multiple cases. For example, 11 of 13 patients who did not progress during the period of observation had stable MM-like scores, and 5 of 7 patients who did progress had MM-scores that increased at the time of progression.</p> <p>The study also uncovered surprising findings about the origins of multiple myeloma. The team estimates based on this study that the earliest genomic changes related to the disease may appear very early in life, in the patient’s 20s or 30s, even though multiple myeloma is typically not diagnosed until much later. </p> <p>To make the MM-like score more clinically accessible, the team is developing a test based on liquid biopsies instead of bone marrow biopsies to collect DNA. This change would potentially enable more frequent monitoring of the evolution of the condition. In addition, the team aims to continue to validate and improve the score by studying more patients over longer periods of time.</p> <p><em>Adapted from <a href="https://www.dana-farber.org/newsroom/news-releases/2025/dana-farber-genomic-score-predicts-progression-to-multiple-myeloma" target="_blank">a press release</a> issued by Dana-Farber Cancer Institute.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the Multiple Myeloma Research Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the International Myeloma Society, Dana-Farber Cancer Institute, the Krouse Family Foundation, the National Cancer Institute, and Stand Up to Cancer. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Alberge J-B, Dutta AK, Poletti A, et al. <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank">Genomic landscape of multiple myeloma and its precursor conditions</a>. <em>Nature Genetics</em>. Online May 21, 2025. DOI: 10.1038/s41588-025-02196-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Tue, 18 Apr 2023 14:51:33 +0000 kzusi@broadinstitute.org 1282071 at /news/researchers-trace-genetic-evolution-chronic-lymphocytic-leukemia-richters-syndrome-0 <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" class="datetime">May 21, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Mutation-based score provides a personalized indicator of disease severity and progression risk, could help inform early intervention strategies</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Elizabeth Dougherty, Dana-Farber Cancer Institute </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" title="Wednesday, May 21, 2025 - 17:00" class="datetime">May 21, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=Vs6PpQYV 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=dWM9v_mQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=8rAVs0u_ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S" alt="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," title="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Multiple myeloma tumor cells (green) </div> </div> </article> </div> </div> </div> </div> </div> </div> <div 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href="/cancer">Cancer Program</a></div> <div class="field__item"><a href="/cancer/cancer-genome-computational-analysis">Cancer Genome Computational Analysis</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-use-genetics-dig-tumors-past" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a 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field--label-hidden">Scientists use genetics to dig into a tumor’s past</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/molecular-map-reveals-insights-genetic-drivers-chronic-lymphocytic-leukemia" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/molecular-map-reveals-insights-genetic-drivers-chronic-lymphocytic-leukemia"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/28696835953_4126c05723_o.jpg?itok=aA_reqDr 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/28696835953_4126c05723_o.jpg?itok=aA_reqDr 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/28696835953_4126c05723_o.jpg?itok=S02gZB-W 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/28696835953_4126c05723_o.jpg?itok=S02gZB-W 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/28696835953_4126c05723_o.jpg?itok=c57QF12J 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/28696835953_4126c05723_o.jpg?itok=xUvQOq4M 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/28696835953_4126c05723_o.jpg?itok=xUvQOq4M" alt="Colorized scanning electron micrograph of a B cell lymphocyte from a human donor." title="Colorized scanning electron micrograph of a B cell lymphocyte from a human donor." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/molecular-map-reveals-insights-genetic-drivers-chronic-lymphocytic-leukemia" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Molecular map reveals insights into the genetic drivers of chronic lymphocytic leukemia</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/immune-system-changes-occur-early-development-multiple-myeloma" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/immune-system-changes-occur-early-development-multiple-myeloma"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=BczEf_qo 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=BczEf_qo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=znO9iHCY 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=znO9iHCY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=vpGL-26K 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=J19UOuqg 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=J19UOuqg" alt="Lauren Solomon, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/immune-system-changes-occur-early-development-multiple-myeloma" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Immune system changes occur early in development of multiple myeloma</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/mathematical-model-finds-cancer-mutations-matter" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/mathematical-model-finds-cancer-mutations-matter"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=EJBMeaUB 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0" alt="Credit: Susanna Hamilton" title="Credit: Susanna Hamilton" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/mathematical-model-finds-cancer-mutations-matter" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Mathematical model finds the cancer mutations that matter</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>A new risk assessment score developed by researchers at Dana-Farber Cancer Institute, the ӳ����ý of MIT and Harvard, and Massachusetts General Hospital reveals how multiple myeloma, a form of blood cancer, begins and progresses from precancerous to malignant states by tracing DNA mutations. The score, called an MM-like score, assesses the severity of disease and risk of progression to active cancer, with higher scores indicating faster progression. In the future, the MM-like score could be used in clinical practice to inform decisions about early intervention. </p> <p>“In patients with a precursor condition for multiple myeloma, the multiple myeloma-like score helps to predict who is at a higher risk of progressing to active cancer,” said co-senior author Jean-Baptiste Alberge, an instructor in medicine at Dana-Farber and postdoctoral scholar at the ӳ����ý. “This study brings us closer to more personalized care for patients with a precursor stage of cancer and could better inform early intervention strategies in the future.”</p> <p>The study was published in <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank"><em>Nature Genetics</em></a>.</p> <p>Multiple myeloma is a cancer in plasma cells that affects 32,000 individuals in the United States each year. Prior to developing multiple myeloma, patients go through precursor stages of the disease called monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). Approximately 1 to 10 percent of patients with these conditions progress to active multiple myeloma per year, with 50-percent of high-risk SMM cases progressing within two years.</p> <p>“There has been an urgent need to identify genomic risk factors that predict disease progression in smoldering myeloma,” said Irene Ghobrial, director of the Center for Early Detection and Interception of Blood Cancers at Dana-Farber and an associate member of the ӳ����ý. “This is especially true as we start early therapeutic interception for high risk SMM. Our data provides a simple genomic score that can help predict progression and can improve on our clinical markers to help stratify risk for our patients.” </p> <p>Existing risk stratification models for multiple myeloma characterize patients as “high” or “low” risk based on measures of tumor burden. These models do not include genetic factors. The MM-like score defined in this study focuses on the presence and progressive evolution of genetic abnormalities to assess the state of the disease. The MM-like score increases over time with the accumulation of mutations that drive the disease. </p> <p>“Treating risk as simply ‘high’ or ‘low’ fails to capture the complexity of tumor timing and evolution, and we saw an opportunity to redefine it through whole-genome sequencing,” said Alberge.</p> <p>Along with co-first authors Ankit Dutta, a postdoctoral fellow in the Ghobrial lab; Andrea Poletti, a post-doctoral fellow at the University of Bologna, Italy; and collaborators from the UK, Germany, and Greece, Alberge compiled mostly whole genome sequencing data from over 1,000 individuals with multiple myeloma and precursor conditions, including 218 patients with MGUS or SMM. The study provides one of the largest analyses of whole genome data for multiple myeloma and its precursor conditions to date.</p> <p>"This study greatly improves our ability to discover both potentially clinically-actionable cancer-driving mutations in MM and the timing of when these events occur across disease states," said <a href="/node/4864">Gad Getz</a>, a core institute member of the ӳ����ý, director of the <a href="/node/45711">Cancer Genome Computational Analysis</a> group in the ӳ����ý’s <a href="/node/8529">Cancer Program</a>, and director of bioinformatics in the Krantz Family Center for Cancer Research and the Department of Pathology at Massachusetts General Hospital. "These insights wouldn't be possible without access to deeply sequenced whole genomes from a large number of patients and across different disease stages."</p> <p>By comparing mutations that were more commonly found in active disease than in asymptomatic precursor forms, they were able to identify genes that are likely linked to the transformation to active disease. The study also revealed the likely order and timing of genetic mutations.</p> <p>To validate the score, the team evaluated 47 tumor samples from 20 patients at various points in the progression of disease. They found that the MM-like scores in individual patients reflected the course of their disease in multiple cases. For example, 11 of 13 patients who did not progress during the period of observation had stable MM-like scores, and 5 of 7 patients who did progress had MM-scores that increased at the time of progression.</p> <p>The study also uncovered surprising findings about the origins of multiple myeloma. The team estimates based on this study that the earliest genomic changes related to the disease may appear very early in life, in the patient’s 20s or 30s, even though multiple myeloma is typically not diagnosed until much later. </p> <p>To make the MM-like score more clinically accessible, the team is developing a test based on liquid biopsies instead of bone marrow biopsies to collect DNA. This change would potentially enable more frequent monitoring of the evolution of the condition. In addition, the team aims to continue to validate and improve the score by studying more patients over longer periods of time.</p> <p><em>Adapted from <a href="https://www.dana-farber.org/newsroom/news-releases/2025/dana-farber-genomic-score-predicts-progression-to-multiple-myeloma" target="_blank">a press release</a> issued by Dana-Farber Cancer Institute.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the Multiple Myeloma Research Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the International Myeloma Society, Dana-Farber Cancer Institute, the Krouse Family Foundation, the National Cancer Institute, and Stand Up to Cancer. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Alberge J-B, Dutta AK, Poletti A, et al. <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank">Genomic landscape of multiple myeloma and its precursor conditions</a>. <em>Nature Genetics</em>. Online May 21, 2025. DOI: 10.1038/s41588-025-02196-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Mon, 09 Jan 2023 16:00:00 +0000 tulrich@broadinstitute.org 1281396 at /news/broad-discovery-center-cambridge-opens-public-october <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" class="datetime">May 21, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Mutation-based score provides a personalized indicator of disease severity and progression risk, could help inform early intervention strategies</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Elizabeth Dougherty, Dana-Farber Cancer Institute </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" title="Wednesday, May 21, 2025 - 17:00" class="datetime">May 21, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=Vs6PpQYV 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=dWM9v_mQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=8rAVs0u_ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S" alt="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," title="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Multiple myeloma tumor cells (green) </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link 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Computational Analysis</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-use-genetics-dig-tumors-past" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/scientists-use-genetics-dig-tumors-past"><picture> <source 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field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/mathematical-model-finds-cancer-mutations-matter"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source 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/> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/mathematical-model-finds-cancer-mutations-matter" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Mathematical model finds the cancer mutations that matter</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>A new risk assessment score developed by researchers at Dana-Farber Cancer Institute, the ӳ����ý of MIT and Harvard, and Massachusetts General Hospital reveals how multiple myeloma, a form of blood cancer, begins and progresses from precancerous to malignant states by tracing DNA mutations. The score, called an MM-like score, assesses the severity of disease and risk of progression to active cancer, with higher scores indicating faster progression. In the future, the MM-like score could be used in clinical practice to inform decisions about early intervention. </p> <p>“In patients with a precursor condition for multiple myeloma, the multiple myeloma-like score helps to predict who is at a higher risk of progressing to active cancer,” said co-senior author Jean-Baptiste Alberge, an instructor in medicine at Dana-Farber and postdoctoral scholar at the ӳ����ý. “This study brings us closer to more personalized care for patients with a precursor stage of cancer and could better inform early intervention strategies in the future.”</p> <p>The study was published in <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank"><em>Nature Genetics</em></a>.</p> <p>Multiple myeloma is a cancer in plasma cells that affects 32,000 individuals in the United States each year. Prior to developing multiple myeloma, patients go through precursor stages of the disease called monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). Approximately 1 to 10 percent of patients with these conditions progress to active multiple myeloma per year, with 50-percent of high-risk SMM cases progressing within two years.</p> <p>“There has been an urgent need to identify genomic risk factors that predict disease progression in smoldering myeloma,” said Irene Ghobrial, director of the Center for Early Detection and Interception of Blood Cancers at Dana-Farber and an associate member of the ӳ����ý. “This is especially true as we start early therapeutic interception for high risk SMM. Our data provides a simple genomic score that can help predict progression and can improve on our clinical markers to help stratify risk for our patients.” </p> <p>Existing risk stratification models for multiple myeloma characterize patients as “high” or “low” risk based on measures of tumor burden. These models do not include genetic factors. The MM-like score defined in this study focuses on the presence and progressive evolution of genetic abnormalities to assess the state of the disease. The MM-like score increases over time with the accumulation of mutations that drive the disease. </p> <p>“Treating risk as simply ‘high’ or ‘low’ fails to capture the complexity of tumor timing and evolution, and we saw an opportunity to redefine it through whole-genome sequencing,” said Alberge.</p> <p>Along with co-first authors Ankit Dutta, a postdoctoral fellow in the Ghobrial lab; Andrea Poletti, a post-doctoral fellow at the University of Bologna, Italy; and collaborators from the UK, Germany, and Greece, Alberge compiled mostly whole genome sequencing data from over 1,000 individuals with multiple myeloma and precursor conditions, including 218 patients with MGUS or SMM. The study provides one of the largest analyses of whole genome data for multiple myeloma and its precursor conditions to date.</p> <p>"This study greatly improves our ability to discover both potentially clinically-actionable cancer-driving mutations in MM and the timing of when these events occur across disease states," said <a href="/node/4864">Gad Getz</a>, a core institute member of the ӳ����ý, director of the <a href="/node/45711">Cancer Genome Computational Analysis</a> group in the ӳ����ý’s <a href="/node/8529">Cancer Program</a>, and director of bioinformatics in the Krantz Family Center for Cancer Research and the Department of Pathology at Massachusetts General Hospital. "These insights wouldn't be possible without access to deeply sequenced whole genomes from a large number of patients and across different disease stages."</p> <p>By comparing mutations that were more commonly found in active disease than in asymptomatic precursor forms, they were able to identify genes that are likely linked to the transformation to active disease. The study also revealed the likely order and timing of genetic mutations.</p> <p>To validate the score, the team evaluated 47 tumor samples from 20 patients at various points in the progression of disease. They found that the MM-like scores in individual patients reflected the course of their disease in multiple cases. For example, 11 of 13 patients who did not progress during the period of observation had stable MM-like scores, and 5 of 7 patients who did progress had MM-scores that increased at the time of progression.</p> <p>The study also uncovered surprising findings about the origins of multiple myeloma. The team estimates based on this study that the earliest genomic changes related to the disease may appear very early in life, in the patient’s 20s or 30s, even though multiple myeloma is typically not diagnosed until much later. </p> <p>To make the MM-like score more clinically accessible, the team is developing a test based on liquid biopsies instead of bone marrow biopsies to collect DNA. This change would potentially enable more frequent monitoring of the evolution of the condition. In addition, the team aims to continue to validate and improve the score by studying more patients over longer periods of time.</p> <p><em>Adapted from <a href="https://www.dana-farber.org/newsroom/news-releases/2025/dana-farber-genomic-score-predicts-progression-to-multiple-myeloma" target="_blank">a press release</a> issued by Dana-Farber Cancer Institute.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the Multiple Myeloma Research Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the International Myeloma Society, Dana-Farber Cancer Institute, the Krouse Family Foundation, the National Cancer Institute, and Stand Up to Cancer. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Alberge J-B, Dutta AK, Poletti A, et al. <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank">Genomic landscape of multiple myeloma and its precursor conditions</a>. <em>Nature Genetics</em>. Online May 21, 2025. DOI: 10.1038/s41588-025-02196-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Mon, 19 Sep 2022 14:53:09 +0000 kzusi@broadinstitute.org 1195701 at /news/study-cancer-immunotherapy-patients-reveals-markers-treatment-response <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" class="datetime">May 21, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Mutation-based score provides a personalized indicator of disease severity and progression risk, could help inform early intervention strategies</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Elizabeth Dougherty, Dana-Farber Cancer Institute </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" title="Wednesday, May 21, 2025 - 17:00" class="datetime">May 21, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=Vs6PpQYV 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=dWM9v_mQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=8rAVs0u_ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S" alt="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," title="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Multiple myeloma tumor cells (green) </div> </div> </article> </div> </div> </div> </div> </div> </div> <div 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width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=znO9iHCY 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=znO9iHCY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=vpGL-26K 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=J19UOuqg 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=J19UOuqg" alt="Lauren Solomon, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/immune-system-changes-occur-early-development-multiple-myeloma" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Immune system changes occur early in development of multiple myeloma</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/mathematical-model-finds-cancer-mutations-matter" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/mathematical-model-finds-cancer-mutations-matter"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=EJBMeaUB 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0" alt="Credit: Susanna Hamilton" title="Credit: Susanna Hamilton" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/mathematical-model-finds-cancer-mutations-matter" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Mathematical model finds the cancer mutations that matter</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>A new risk assessment score developed by researchers at Dana-Farber Cancer Institute, the ӳ����ý of MIT and Harvard, and Massachusetts General Hospital reveals how multiple myeloma, a form of blood cancer, begins and progresses from precancerous to malignant states by tracing DNA mutations. The score, called an MM-like score, assesses the severity of disease and risk of progression to active cancer, with higher scores indicating faster progression. In the future, the MM-like score could be used in clinical practice to inform decisions about early intervention. </p> <p>“In patients with a precursor condition for multiple myeloma, the multiple myeloma-like score helps to predict who is at a higher risk of progressing to active cancer,” said co-senior author Jean-Baptiste Alberge, an instructor in medicine at Dana-Farber and postdoctoral scholar at the ӳ����ý. “This study brings us closer to more personalized care for patients with a precursor stage of cancer and could better inform early intervention strategies in the future.”</p> <p>The study was published in <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank"><em>Nature Genetics</em></a>.</p> <p>Multiple myeloma is a cancer in plasma cells that affects 32,000 individuals in the United States each year. Prior to developing multiple myeloma, patients go through precursor stages of the disease called monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). Approximately 1 to 10 percent of patients with these conditions progress to active multiple myeloma per year, with 50-percent of high-risk SMM cases progressing within two years.</p> <p>“There has been an urgent need to identify genomic risk factors that predict disease progression in smoldering myeloma,” said Irene Ghobrial, director of the Center for Early Detection and Interception of Blood Cancers at Dana-Farber and an associate member of the ӳ����ý. “This is especially true as we start early therapeutic interception for high risk SMM. Our data provides a simple genomic score that can help predict progression and can improve on our clinical markers to help stratify risk for our patients.” </p> <p>Existing risk stratification models for multiple myeloma characterize patients as “high” or “low” risk based on measures of tumor burden. These models do not include genetic factors. The MM-like score defined in this study focuses on the presence and progressive evolution of genetic abnormalities to assess the state of the disease. The MM-like score increases over time with the accumulation of mutations that drive the disease. </p> <p>“Treating risk as simply ‘high’ or ‘low’ fails to capture the complexity of tumor timing and evolution, and we saw an opportunity to redefine it through whole-genome sequencing,” said Alberge.</p> <p>Along with co-first authors Ankit Dutta, a postdoctoral fellow in the Ghobrial lab; Andrea Poletti, a post-doctoral fellow at the University of Bologna, Italy; and collaborators from the UK, Germany, and Greece, Alberge compiled mostly whole genome sequencing data from over 1,000 individuals with multiple myeloma and precursor conditions, including 218 patients with MGUS or SMM. The study provides one of the largest analyses of whole genome data for multiple myeloma and its precursor conditions to date.</p> <p>"This study greatly improves our ability to discover both potentially clinically-actionable cancer-driving mutations in MM and the timing of when these events occur across disease states," said <a href="/node/4864">Gad Getz</a>, a core institute member of the ӳ����ý, director of the <a href="/node/45711">Cancer Genome Computational Analysis</a> group in the ӳ����ý’s <a href="/node/8529">Cancer Program</a>, and director of bioinformatics in the Krantz Family Center for Cancer Research and the Department of Pathology at Massachusetts General Hospital. "These insights wouldn't be possible without access to deeply sequenced whole genomes from a large number of patients and across different disease stages."</p> <p>By comparing mutations that were more commonly found in active disease than in asymptomatic precursor forms, they were able to identify genes that are likely linked to the transformation to active disease. The study also revealed the likely order and timing of genetic mutations.</p> <p>To validate the score, the team evaluated 47 tumor samples from 20 patients at various points in the progression of disease. They found that the MM-like scores in individual patients reflected the course of their disease in multiple cases. For example, 11 of 13 patients who did not progress during the period of observation had stable MM-like scores, and 5 of 7 patients who did progress had MM-scores that increased at the time of progression.</p> <p>The study also uncovered surprising findings about the origins of multiple myeloma. The team estimates based on this study that the earliest genomic changes related to the disease may appear very early in life, in the patient’s 20s or 30s, even though multiple myeloma is typically not diagnosed until much later. </p> <p>To make the MM-like score more clinically accessible, the team is developing a test based on liquid biopsies instead of bone marrow biopsies to collect DNA. This change would potentially enable more frequent monitoring of the evolution of the condition. In addition, the team aims to continue to validate and improve the score by studying more patients over longer periods of time.</p> <p><em>Adapted from <a href="https://www.dana-farber.org/newsroom/news-releases/2025/dana-farber-genomic-score-predicts-progression-to-multiple-myeloma" target="_blank">a press release</a> issued by Dana-Farber Cancer Institute.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the Multiple Myeloma Research Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the International Myeloma Society, Dana-Farber Cancer Institute, the Krouse Family Foundation, the National Cancer Institute, and Stand Up to Cancer. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Alberge J-B, Dutta AK, Poletti A, et al. <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank">Genomic landscape of multiple myeloma and its precursor conditions</a>. <em>Nature Genetics</em>. Online May 21, 2025. DOI: 10.1038/s41588-025-02196-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Mon, 12 Sep 2022 15:06:37 +0000 adicorat 1176511 at /news/molecular-map-reveals-insights-genetic-drivers-chronic-lymphocytic-leukemia <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" class="datetime">May 21, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Mutation-based score provides a personalized indicator of disease severity and progression risk, could help inform early intervention strategies</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Elizabeth Dougherty, Dana-Farber Cancer Institute </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" title="Wednesday, May 21, 2025 - 17:00" class="datetime">May 21, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1601px) 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height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S" alt="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," title="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Multiple myeloma tumor cells (green) </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/28696835953_4126c05723_o.jpg?itok=xUvQOq4M 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/28696835953_4126c05723_o.jpg?itok=xUvQOq4M" alt="Colorized scanning electron micrograph of a B cell lymphocyte from a human donor." title="Colorized scanning electron micrograph of a B cell lymphocyte from a human donor." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/molecular-map-reveals-insights-genetic-drivers-chronic-lymphocytic-leukemia" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Molecular map reveals insights into the genetic drivers of chronic lymphocytic leukemia</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/immune-system-changes-occur-early-development-multiple-myeloma" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/immune-system-changes-occur-early-development-multiple-myeloma"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=BczEf_qo 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=BczEf_qo 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=znO9iHCY 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=znO9iHCY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=vpGL-26K 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=J19UOuqg 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=J19UOuqg" alt="Lauren Solomon, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/immune-system-changes-occur-early-development-multiple-myeloma" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Immune system changes occur early in development of multiple myeloma</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/mathematical-model-finds-cancer-mutations-matter" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/mathematical-model-finds-cancer-mutations-matter"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=EJBMeaUB 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0" alt="Credit: Susanna Hamilton" title="Credit: Susanna Hamilton" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/mathematical-model-finds-cancer-mutations-matter" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Mathematical model finds the cancer mutations that matter</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>A new risk assessment score developed by researchers at Dana-Farber Cancer Institute, the ӳ����ý of MIT and Harvard, and Massachusetts General Hospital reveals how multiple myeloma, a form of blood cancer, begins and progresses from precancerous to malignant states by tracing DNA mutations. The score, called an MM-like score, assesses the severity of disease and risk of progression to active cancer, with higher scores indicating faster progression. In the future, the MM-like score could be used in clinical practice to inform decisions about early intervention. </p> <p>“In patients with a precursor condition for multiple myeloma, the multiple myeloma-like score helps to predict who is at a higher risk of progressing to active cancer,” said co-senior author Jean-Baptiste Alberge, an instructor in medicine at Dana-Farber and postdoctoral scholar at the ӳ����ý. “This study brings us closer to more personalized care for patients with a precursor stage of cancer and could better inform early intervention strategies in the future.”</p> <p>The study was published in <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank"><em>Nature Genetics</em></a>.</p> <p>Multiple myeloma is a cancer in plasma cells that affects 32,000 individuals in the United States each year. Prior to developing multiple myeloma, patients go through precursor stages of the disease called monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). Approximately 1 to 10 percent of patients with these conditions progress to active multiple myeloma per year, with 50-percent of high-risk SMM cases progressing within two years.</p> <p>“There has been an urgent need to identify genomic risk factors that predict disease progression in smoldering myeloma,” said Irene Ghobrial, director of the Center for Early Detection and Interception of Blood Cancers at Dana-Farber and an associate member of the ӳ����ý. “This is especially true as we start early therapeutic interception for high risk SMM. Our data provides a simple genomic score that can help predict progression and can improve on our clinical markers to help stratify risk for our patients.” </p> <p>Existing risk stratification models for multiple myeloma characterize patients as “high” or “low” risk based on measures of tumor burden. These models do not include genetic factors. The MM-like score defined in this study focuses on the presence and progressive evolution of genetic abnormalities to assess the state of the disease. The MM-like score increases over time with the accumulation of mutations that drive the disease. </p> <p>“Treating risk as simply ‘high’ or ‘low’ fails to capture the complexity of tumor timing and evolution, and we saw an opportunity to redefine it through whole-genome sequencing,” said Alberge.</p> <p>Along with co-first authors Ankit Dutta, a postdoctoral fellow in the Ghobrial lab; Andrea Poletti, a post-doctoral fellow at the University of Bologna, Italy; and collaborators from the UK, Germany, and Greece, Alberge compiled mostly whole genome sequencing data from over 1,000 individuals with multiple myeloma and precursor conditions, including 218 patients with MGUS or SMM. The study provides one of the largest analyses of whole genome data for multiple myeloma and its precursor conditions to date.</p> <p>"This study greatly improves our ability to discover both potentially clinically-actionable cancer-driving mutations in MM and the timing of when these events occur across disease states," said <a href="/node/4864">Gad Getz</a>, a core institute member of the ӳ����ý, director of the <a href="/node/45711">Cancer Genome Computational Analysis</a> group in the ӳ����ý’s <a href="/node/8529">Cancer Program</a>, and director of bioinformatics in the Krantz Family Center for Cancer Research and the Department of Pathology at Massachusetts General Hospital. "These insights wouldn't be possible without access to deeply sequenced whole genomes from a large number of patients and across different disease stages."</p> <p>By comparing mutations that were more commonly found in active disease than in asymptomatic precursor forms, they were able to identify genes that are likely linked to the transformation to active disease. The study also revealed the likely order and timing of genetic mutations.</p> <p>To validate the score, the team evaluated 47 tumor samples from 20 patients at various points in the progression of disease. They found that the MM-like scores in individual patients reflected the course of their disease in multiple cases. For example, 11 of 13 patients who did not progress during the period of observation had stable MM-like scores, and 5 of 7 patients who did progress had MM-scores that increased at the time of progression.</p> <p>The study also uncovered surprising findings about the origins of multiple myeloma. The team estimates based on this study that the earliest genomic changes related to the disease may appear very early in life, in the patient’s 20s or 30s, even though multiple myeloma is typically not diagnosed until much later. </p> <p>To make the MM-like score more clinically accessible, the team is developing a test based on liquid biopsies instead of bone marrow biopsies to collect DNA. This change would potentially enable more frequent monitoring of the evolution of the condition. In addition, the team aims to continue to validate and improve the score by studying more patients over longer periods of time.</p> <p><em>Adapted from <a href="https://www.dana-farber.org/newsroom/news-releases/2025/dana-farber-genomic-score-predicts-progression-to-multiple-myeloma" target="_blank">a press release</a> issued by Dana-Farber Cancer Institute.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the Multiple Myeloma Research Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the International Myeloma Society, Dana-Farber Cancer Institute, the Krouse Family Foundation, the National Cancer Institute, and Stand Up to Cancer. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Alberge J-B, Dutta AK, Poletti A, et al. <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank">Genomic landscape of multiple myeloma and its precursor conditions</a>. <em>Nature Genetics</em>. Online May 21, 2025. DOI: 10.1038/s41588-025-02196-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Thu, 04 Aug 2022 16:53:54 +0000 kzusi@broadinstitute.org 1157391 at /news/immune-system-changes-occur-early-development-multiple-myeloma <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" class="datetime">May 21, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Genomic score predicts patients' progression to multiple myeloma</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Mutation-based score provides a personalized indicator of disease severity and progression risk, could help inform early intervention strategies</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Elizabeth Dougherty, Dana-Farber Cancer Institute </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-05-21T17:00:58-04:00" title="Wednesday, May 21, 2025 - 17:00" class="datetime">May 21, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=d4G6IQ6d 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=Vs6PpQYV 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=dWM9v_mQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=8rAVs0u_ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/multiple_myeloma_nci-vol-10565-300_crop.jpeg?itok=vLTrUc0S" alt="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," title="A fluorescent microscopy image showing multiple myeloma cells colored green and bone cells colored red, growing on an artificial scaffold colored purple," typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Multiple myeloma tumor cells (green) </div> </div> </article> </div> </div> </div> </div> </div> </div> <div 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href="/cancer">Cancer Program</a></div> <div class="field__item"><a href="/cancer/cancer-genome-computational-analysis">Cancer Genome Computational Analysis</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/scientists-use-genetics-dig-tumors-past" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/scientists-use-genetics-dig-tumors-past"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/0423_Getz_News_Story_02.png?itok=uX6ZWyQk 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/0423_Getz_News_Story_02.png?itok=uX6ZWyQk 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/0423_Getz_News_Story_02.png?itok=K8WtxKFg 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/0423_Getz_News_Story_02.png?itok=K8WtxKFg 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" 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width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=znO9iHCY 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=znO9iHCY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=vpGL-26K 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=J19UOuqg 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Single-cell-multiple-myeloma2.jpg?h=d3e04ee7&itok=J19UOuqg" alt="Lauren Solomon, ӳ����ý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/immune-system-changes-occur-early-development-multiple-myeloma" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Immune system changes occur early in development of multiple myeloma</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/mathematical-model-finds-cancer-mutations-matter" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/mathematical-model-finds-cancer-mutations-matter"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=mG8prOEF 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=j4FaNHey 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=EJBMeaUB 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/drivers_passengers_v2.jpg?h=d3e04ee7&itok=bP9JroV0" alt="Credit: Susanna Hamilton" title="Credit: Susanna Hamilton" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/mathematical-model-finds-cancer-mutations-matter" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Mathematical model finds the cancer mutations that matter</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>A new risk assessment score developed by researchers at Dana-Farber Cancer Institute, the ӳ����ý of MIT and Harvard, and Massachusetts General Hospital reveals how multiple myeloma, a form of blood cancer, begins and progresses from precancerous to malignant states by tracing DNA mutations. The score, called an MM-like score, assesses the severity of disease and risk of progression to active cancer, with higher scores indicating faster progression. In the future, the MM-like score could be used in clinical practice to inform decisions about early intervention. </p> <p>“In patients with a precursor condition for multiple myeloma, the multiple myeloma-like score helps to predict who is at a higher risk of progressing to active cancer,” said co-senior author Jean-Baptiste Alberge, an instructor in medicine at Dana-Farber and postdoctoral scholar at the ӳ����ý. “This study brings us closer to more personalized care for patients with a precursor stage of cancer and could better inform early intervention strategies in the future.”</p> <p>The study was published in <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank"><em>Nature Genetics</em></a>.</p> <p>Multiple myeloma is a cancer in plasma cells that affects 32,000 individuals in the United States each year. Prior to developing multiple myeloma, patients go through precursor stages of the disease called monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). Approximately 1 to 10 percent of patients with these conditions progress to active multiple myeloma per year, with 50-percent of high-risk SMM cases progressing within two years.</p> <p>“There has been an urgent need to identify genomic risk factors that predict disease progression in smoldering myeloma,” said Irene Ghobrial, director of the Center for Early Detection and Interception of Blood Cancers at Dana-Farber and an associate member of the ӳ����ý. “This is especially true as we start early therapeutic interception for high risk SMM. Our data provides a simple genomic score that can help predict progression and can improve on our clinical markers to help stratify risk for our patients.” </p> <p>Existing risk stratification models for multiple myeloma characterize patients as “high” or “low” risk based on measures of tumor burden. These models do not include genetic factors. The MM-like score defined in this study focuses on the presence and progressive evolution of genetic abnormalities to assess the state of the disease. The MM-like score increases over time with the accumulation of mutations that drive the disease. </p> <p>“Treating risk as simply ‘high’ or ‘low’ fails to capture the complexity of tumor timing and evolution, and we saw an opportunity to redefine it through whole-genome sequencing,” said Alberge.</p> <p>Along with co-first authors Ankit Dutta, a postdoctoral fellow in the Ghobrial lab; Andrea Poletti, a post-doctoral fellow at the University of Bologna, Italy; and collaborators from the UK, Germany, and Greece, Alberge compiled mostly whole genome sequencing data from over 1,000 individuals with multiple myeloma and precursor conditions, including 218 patients with MGUS or SMM. The study provides one of the largest analyses of whole genome data for multiple myeloma and its precursor conditions to date.</p> <p>"This study greatly improves our ability to discover both potentially clinically-actionable cancer-driving mutations in MM and the timing of when these events occur across disease states," said <a href="/node/4864">Gad Getz</a>, a core institute member of the ӳ����ý, director of the <a href="/node/45711">Cancer Genome Computational Analysis</a> group in the ӳ����ý’s <a href="/node/8529">Cancer Program</a>, and director of bioinformatics in the Krantz Family Center for Cancer Research and the Department of Pathology at Massachusetts General Hospital. "These insights wouldn't be possible without access to deeply sequenced whole genomes from a large number of patients and across different disease stages."</p> <p>By comparing mutations that were more commonly found in active disease than in asymptomatic precursor forms, they were able to identify genes that are likely linked to the transformation to active disease. The study also revealed the likely order and timing of genetic mutations.</p> <p>To validate the score, the team evaluated 47 tumor samples from 20 patients at various points in the progression of disease. They found that the MM-like scores in individual patients reflected the course of their disease in multiple cases. For example, 11 of 13 patients who did not progress during the period of observation had stable MM-like scores, and 5 of 7 patients who did progress had MM-scores that increased at the time of progression.</p> <p>The study also uncovered surprising findings about the origins of multiple myeloma. The team estimates based on this study that the earliest genomic changes related to the disease may appear very early in life, in the patient’s 20s or 30s, even though multiple myeloma is typically not diagnosed until much later. </p> <p>To make the MM-like score more clinically accessible, the team is developing a test based on liquid biopsies instead of bone marrow biopsies to collect DNA. This change would potentially enable more frequent monitoring of the evolution of the condition. In addition, the team aims to continue to validate and improve the score by studying more patients over longer periods of time.</p> <p><em>Adapted from <a href="https://www.dana-farber.org/newsroom/news-releases/2025/dana-farber-genomic-score-predicts-progression-to-multiple-myeloma" target="_blank">a press release</a> issued by Dana-Farber Cancer Institute.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the Multiple Myeloma Research Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the International Myeloma Society, Dana-Farber Cancer Institute, the Krouse Family Foundation, the National Cancer Institute, and Stand Up to Cancer. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Alberge J-B, Dutta AK, Poletti A, et al. <a href="https://www.nature.com/articles/s41588-025-02196-0" target="_blank">Genomic landscape of multiple myeloma and its precursor conditions</a>. <em>Nature Genetics</em>. Online May 21, 2025. DOI: 10.1038/s41588-025-02196-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Mon, 27 Apr 2020 15:07:19 +0000 tulrich@broadinstitute.org 628281 at