Chromosomal instability selects gene copy-number variants encoding core regulators of proliferation in ER+ breast cancer.

ABSTRACT: Chromosomal instability (CIN) is associated with poor outcome in epithelial malignancies, including breast carcinomas. Evidence suggests that prognostic signatures in estrogen receptor-positive (ER(+)) breast cancer define tumors with CIN and high proliferative potential. Intriguingly, CIN induction in lower eukaryotic cells and human cells is context dependent, typically resulting in a proliferation disadvantage but conferring a fitness benefit under strong selection pressures. We hypothesized that CIN permits accelerated genomic evolution through the generation of diverse DNA copy-number events that may be selected during disease development. In support of this hypothesis, we found evidence for selection of gene amplification of core regulators of proliferation in CIN-associated cancer g

SUBMITTER: Endesfelder D 

PROVIDER: S-EPMC4167338 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature