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<https://discovery.ucl.ac.uk/id/eprint/10205446> <http://purl.org/dc/terms/title> "Chromosomal instability selects gene copy number variants\r\nencoding core regulators of proliferation in ER+ breast cancer"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10205446> <http://purl.org/ontology/bibo/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 genomes. Stable DNA copy-number amplifications of the core regulators TPX2 and UBE2C were associated with expression of a gene module involved in proliferation. The module genes were enriched within prognostic signature gene sets for ER+ breast cancer, providing a logical connection between CIN and prognostic signature expression. Our results provide a framework to decipher the impact of intratumor heterogeneity on key cancer phenotypes, and they suggest that CIN provides a permissive landscape for selection of copy-number alterations that drive cancer proliferation."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10205446> <http://purl.org/dc/terms/date> "2014-09-01" .
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