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Integrated Profiling of Basal and Luminal Breast Cancers

¹ Marseille Cancer Research Center, Institut Paoli-Calmettes and UMR599 Institut National de la Santé et de la Recherche Médicale, Department of Molecular Oncology, ² Department of Biopathology, and ³ Department of Medical Oncology, Institut Paoli-Calmettes; ⁴ Université de la Méditerranée; ⁵ Institut de Médecine Tropicale du Service de Santé des Armées, Unité de Recherche en Pharmacologie et Physiopathologie Parasitaire, Marseille, France; and ⁶ Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands

Requests for reprints: Max Chaffanet, Department of Molecular Oncology, Institut Paoli-Calmettes, 232 Bd. Sainte Marguerite, 13009 Marseille, France. Phone: 33-4-91-22-34-77; Fax: 33-4-91-22-35-44; E-mail: chaffanetm{at}marseille.fnclcc.fr or Daniel Birnbaum, UMR599 Institut National de la Sante et de la Recherche Medicale, 27 Bd. Leï Roure, 13009 Marseille, France. Phone: 33-4-91-75-84-07; E-mail: birnbaum{at}marseille.inserm.fr.

Basal and luminal are two molecular subtypes of breast cancer with opposite histoclinical features. We report a combined, high-resolution analysis of genome copy number and gene expression in primary basal and luminal breast cancers. First, we identified and compared genomic alterations in 45 basal and 48 luminal tumors by using 244K oligonucleotide array comparative genomic hybridization (aCGH). We found various genome gains and losses and rare high-level gene amplifications that may provide therapeutic targets. We show that gain of 10p is a new alteration in basal breast cancer and that a subregion of the 8p12 amplification is specific of luminal tumors. Rare high-level amplifications contained BCL2L2, CCNE, EGFR, FGFR2, IGF1R, NOTCH2, and PIK3CA. Potential gene breaks involved ETV6 and FLT3. Second, we analyzed both aCGH and gene expression profiles for 42 basal and 32 luminal breast cancers. The results support the existence of specific oncogenic pathways in basal and luminal breast cancers, involving several potential oncogenes and tumor suppressor genes (TSG). In basal tumors, 73 candidate oncogenes were identified in chromosome regions 1q21-23, 10p14, and 12p13 and 28 candidate TSG in regions 4q32-34 and 5q11-23. In luminal breast cancers, 33 potential oncogenes were identified in 1q21-23, 8p12-q21, 11q13, and 16p12-13 and 61 candidate TSG in 16q12-13, 16q22-24, and 17p13. HORMAD1 (P = 6.5 x 10^–5) and ZNF703 (P = 7 x 10^–4) were the most significant basal and luminal potential oncogenes, respectively. Finally, among 10p candidate oncogenes associated with basal subtype, we validated CDC123/C10orf7 protein as a basal marker. [Cancer Res 2007;67(24):11565–75]

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