Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene‐expression subtypes of breast cancer

Genes Chromosomes and Cancer - Tập 45 Số 11 - Trang 1033-1040 - 2006
Anna Bergamaschi1,2, Young Ho Kim2, Pei Wang3, Thérese Sørlie1, Tina Hernandez‐Boussard4, Per Eystein Lønning5, Robert Tibshirani3,6, Anne‐Lise Børresen‐Dale1,7, Jonathan R. Pollack2
1Department of Genetics, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
2Department of Pathology, Stanford University, Stanford, California
3Department of Statistics, Stanford University, Stanford, California
4Department of Biochemistry, Stanford University, Stanford, California
5Department of Medicine (Oncology), Haukeland University Hospital, Bergen, Norway
6Health Research & Policy, Stanford University, Stanford, California
7Medical Faculty, University of Oslo, Oslo, Norway

Tóm tắt

AbstractBreast 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. © 2006 Wiley‐Liss, Inc.

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Genes Chromosomes and Cancer

Tập 45 Số 11

1033-1040

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