Functional Genomic Landscape of Human Breast Cancer Drivers, Vulnerabilities, and Resistance.

ABSTRACT: Large-scale genomic studies have identified multiple somatic aberrations in breast cancer, including copy number alterations and point mutations. Still, identifying causal variants and emergent vulnerabilities that arise as a consequence of genetic alterations remain major challenges. We performed whole-genome small hairpin RNA (shRNA) "dropout screens" on 77 breast cancer cell lines. Using a hierarchical linear regression algorithm to score our screen results and integrate them with accompanying detailed genetic and proteomic information, we identify vulnerabilities in breast cancer, including candidate "drivers," and reveal general functional genomic properties of cancer cells. Comparisons of gene essentiality with drug sensitivity data suggest potential resistance mechanisms, effects of

SUBMITTER: Marcotte R 

PROVIDER: S-EPMC4724865 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature