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Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene‐expression subtypes of breast cancer
Author(s) -
Bergamaschi Anna,
Kim Young H.,
Wang Pei,
Sørlie Therese,
HernandezBoussard Tina,
Lonning Per E.,
Tibshirani Robert,
BørresenDale AnneLise,
Pollack Jonathan R.
Publication year - 2006
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20366
Subject(s) - breast cancer , comparative genomic hybridization , copy number analysis , copy number variation , biology , genome instability , cancer , gene expression profiling , cancer research , chromosome instability , gene , oncology , bioinformatics , genetics , medicine , genome , gene expression , dna , dna damage , chromosome
Breast cancer is a leading cause of cancer-death among women, where the clinicopathological features of tumors are used to prognosticate and guide therapy. DNA copy number alterations (CNAs), which occur frequently in breast cancer and define key pathogenetic events, are also potentially useful prognostic or predictive factors. Here, we report a genome-wide array-based comparative genomic hybridization (array CGH) survey of CNAs in 89 breast tumors from a patient cohort with locally advanced disease. Statistical analysis links distinct cytoband loci harboring CNAs to specific clinicopathological parameters, including tumor grade, estrogen receptor status, presence of TP53 mutation, and overall survival. Notably, distinct spectra of CNAs also underlie the different subtypes of breast cancer recently defined by expression-profiling, implying these subtypes develop along distinct genetic pathways. In addition, higher numbers of gains/losses are associated with the "basal-like" tumor subtype, while high-level DNA amplification is more frequent in "luminal-B" subtype tumors, suggesting also that distinct mechanisms of genomic instability might underlie their pathogenesis. The identified CNAs may provide a basis for improved patient prognostication, as well as a starting point to define important genes to further our understanding of the pathobiology of breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat