Megan Tandar
Megan, a rising junior studying chemistry and asian american diaspora studies at Duke University, utilized computational methods to identify functional vulnerabilities present in extrachromosomal DNA-containing cancers.
Recent research has demonstrated the role of extrachromosomal DNA (ecDNA) in driving cancer metastasis and poor treatment response, with approximately 17% of tumors containing high proportions of ecDNA. My summer at the Ó³»´«Ã½ was transformative in so many ways that I truly couldn’t have predicted. Scientifically - I gained so many essential technical and communication skills, and heard from amazing researchers on how their work drives change. On a personal level, I discovered so much about myself, the paths science can pave, and found vibrant friendships in the brilliant peers of my cohort. BSRP left me with a deep sense of inspiration and a stronger commitment to science as a community to contribute to, learn from, and grow with.Despite this known clinical relevance, functional dependencies of ecDNA+ tumors remain largely uncharacterized. To identify vulnerabilities, we leveraged whole-genome sequencing from the Cancer Cell Line Encyclopedia to investigate structural features and oncogenes under positive selection in ecDNA+ tumors. We then integrated gene essentiality data from DepMap to evaluate the functional impact of these features, allowing for subsequent identification of ecDNA-conferred essential genes and effective drugs.
Our results revealed widespread ecDNA presence across many cancer types, including high prevalence in lung, breast, and ovarian cancers. In ovarian cancer, CRISPR and drug screens identified a subset of genes as more essential in ecDNA+ tumors, which may represent potential pharmaceutical targets for ecDNA+ cancers. We aim to continue investigating these genes through evaluation of the structural complexities in ecDNA. Ultimately, this project aims to lay foundational knowledge for ecDNA-driven functional vulnerabilities, informing targeted cancer therapies and treatment plans.
Project: Characterizing Functional Vulnerabilities of Extrachromosomal DNA in Cancer
Mentor: Ignacio Vázquez-GarcÃa, Vázquez-GarcÃa Lab, Massachusetts General Hospital Department of Molecular Pathology, Harvard Medical School
