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Cancer Genes and Genomics

Comprehensive Profiling of 8p11-12 Amplification in Breast Cancer

¹ Marseilles Cancer Institute, Department of Molecular Oncology, UMR599 Institut National de la Sante et de la Recherche Medicale and Institut Paoli-Calmettes; ² Department of Biostatistics, UMR599 and Institut Paoli-Calmettes; ³ Department of BioPathology, Institut Paoli-Calmettes, Marseilles, France; ⁴ EMI229 Institut National de la Sante et de la Recherche Medicale and ⁵ Department of Pathology, CRLC Val d'Aurelle-Paul Lamarque, Montpellier, France; ⁶ Laboratory of Cytogenetics, Centre Hospitalier Universitaire of Rennes, Rennes, France; and ⁷ Karmanos Institute, Detroit, Michigan

Requests for reprints: Daniel Birnbaum, UMR599 Institut National de la Sante et de la Recherche Medicale, 27 Bd. Leï Roure, 13009 Marseilles, France. Phone: 33-4-91-75-84-07; Fax: 33-4-91-26-03-64. E-mail: birnbaum{at}marseille.inserm.fr

In human carcinomas, especially breast cancer, chromosome arm 8p is frequently involved in complex chromosomal rearrangements that combine amplification at 8p11-12, break in the 8p12-21 region, and loss of 8p21-ter. Several studies have identified putative oncogenes in the 8p11-12 amplicon. However, discrepancies and the lack of knowledge on the structure of this amplification lead us to think that the actual identity of the oncogenes is not definitively established. We present here a comprehensive study combining genomic, expression, and chromosome break analyses of the 8p11-12 region in breast cell lines and primary breast tumors. We show the existence of four amplicons at 8p11-12 using array comparative genomic hybridization. Gene expression analysis of 123 samples using DNA microarrays identified 14 genes significantly overexpressed in relation to amplification. Using fluorescence in situ hybridization analysis on tissue microarrays, we show the existence of a cluster of breakpoints spanning a region just telomeric to and associated with the amplification. Finally, we show that 8p11-12 amplification has a pejorative effect on survival in breast cancer. (Mol Cancer Res 2005;3(12):655–67)

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