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Across-species comprehensive copy number analyses identifies subtype-specific drivers of breast cancer development

ABSTRACT: A large number of DNA copy number alterations (CNAs) exist in human breast cancers, and thus characterizing the most frequent ones is key to advancing therapeutics because it is likely that these recurrent CNAs contain breast tumor ‘drivers’ (i.e. causal genes). Here, we have comprehensively profiled a large set of human breast tumors and mouse models of mammary cancers using DNA copy number and gene expression microarrays. By using an across species genetic conservation approach, we identified common altered regions/genes that were similarly altered in both human and mouse breast tumors; additionally, we further demonstrate that many of these conserved CNA regions are also expression-subtype specific, such as the common gain of 1q21-23, or loss of 5q in mouse and human Basal-like cancers. Published functional studies further validated likely driver genes from these regions including Nicastrin (NCSTN) on 1q23 in Basal-like breast cancers. The ability to integrate copy number, and expression data, from mouse and human breast tumors identified at least 25 regions of shared subtype specific alternations, which has identified a number of known drivers and a few regions that merit additional studies.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE52173 | GEO | 2014/12/31

SECONDARY ACCESSION(S): PRJNA227098

REPOSITORIES: GEO

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