Integrative eQTL-Based Analyses Reveal the Biology of Breast Cancer Risk Loci

Menée sur des données d'expression génique issues du projet "The Cancer Genome Atlas", cette étude met en œuvre une méthode d'analyse de liaison génétique dite eQTL pour identifier des gènes candidats dans 6 loci de susceptibilité au cancer du sein

Résumé en anglais

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.
º A method to identify eQTLs from tumors by adjusting for somatic alterations
º Application of method to The Cancer Genome Atlas (TCGA) breast cancer data set
º Discovery of candidate causal genes for 6 breast cancer risk loci

An eQTL-based method discriminates between germline versus somatic contributions to gene expression changes in breast cancer and identifies candidate causal genes for 6 risk loci.