Comprehensive Profiling of 8p11-12 Amplification in Breast Cancer

• Published in: Molecular cancer research Vol. 3; no. 12; pp. 655 - 667
• Main Authors: Gelsi-Boyer, Véronique, Orsetti, Béatrice, Cervera, Nathalie, Finetti, Pascal, Sircoulomb, Fabrice, Rougé, Carole, Lasorsa, Laurence, Letessier, Anne, Ginestier, Christophe, Monville, Florence, Esteyriès, Séverine, Adélaïde, José, Esterni, Benjamin, Henry, Catherine, Ethier, Stephen P, Bibeau, Frédéric, Mozziconacci, Marie-Joëlle, Charafe-Jauffret, Emmanuelle, Jacquemier, Jocelyne, Bertucci, François, Birnbaum, Daniel, Theillet, Charles, Chaffanet, Max
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01.12.2005
• Subjects: 8p12; aCGH; Biochemistry, Molecular Biology; Biotechnology; breast cancer; Breast Neoplasms; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cell Line, Tumor; chromosome 8; Chromosome Aberrations; Chromosomes, Human, Pair 8; Chromosomes, Human, Pair 8 - genetics; Chromosomes, Human, Pair 8 - metabolism; DNA amplification; DNA Damage; DNA microarrays; FISH; Gene Amplification; Genomics; Humans; In Situ Hybridization, Fluorescence; Life Sciences; Middle Aged; Oligonucleotide Array Sequence Analysis; Oncogenes; Oncogenes - genetics; Telomere; Telomere - genetics; Tissue Array An; Tissue Array Analysis; tissue microarrays; tissue microarrays; 8p12; DNA microarrays; FISH; Breast cancer; DNA amplification; chromosome 8; array-CGH
• ISSN: 1541-7786; 1557-3125
• DOI: 10.1158/1541-7786.MCR-05-0128

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)