Integrative eQTL-based analyses reveal the biology of breast cancer risk loci.
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| Abstract | Germline determinants of gene expression in tumors are infrequently studied due to the complexity of transcript regulation caused by somatically acquired alterations. We performed expression quantitative trait locus (eQTL)-based analyses using the multi-level information provided in The Cancer Genome Atlas (TCGA). Of the factors we measured, cis-acting eQTLs accounted for 1.2% of the total variation of tumor gene expression, while somatic copy-number alteration and CpG methylation accounted for 7.3% and 3.3%, respectively. eQTL analyses of 15 previously reported breast cancer risk loci resulted in the discovery of three variants that are significantly associated with transcript levels (false discovery rate [FDR] 0.1). Our trans-based analysis identified an additional three risk loci to act through ESR1, MYC, and KLF4. These findings provide a more comprehensive picture of gene expression determinants in breast cancer as well as insights into the underlying biology of breast cancer risk loci. |
| Year of Publication | 2013
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| Journal | Cell
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| Volume | 152
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| Issue | 3
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| Pages | 633-41
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| Date Published | 2013 Jan 31
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| ISSN | 1097-4172
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| URL | |
| DOI | 10.1016/j.cell.2012.12.034
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| PubMed ID | 23374354
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| PubMed Central ID | PMC4165609
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| Grant list | R01 CA129435 / CA / NCI NIH HHS / United States
R01 CA131341 / CA / NCI NIH HHS / United States
U19 CA148537 / CA / NCI NIH HHS / United States
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