title: Comprehensive profiling of 8p11-12 amplification in breast cancer.
abstract: 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.
authors.affiliation: Marseilles Cancer Institute, Department of Molecular Oncology, UMR599 Institut National de la Sante et de la Recherche Medicale, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Gelsi-Boyer
authors.forename: Béatrice
authors.initials: B
authors.lastname: Orsetti
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cervera
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Fabrice
authors.initials: F
authors.lastname: Sircoulomb
authors.forename: Carole
authors.initials: C
authors.lastname: Rougé
authors.forename: Laurence
authors.initials: L
authors.lastname: Lasorsa
authors.forename: Anne
authors.initials: A
authors.lastname: Letessier
authors.forename: Christophe
authors.initials: C
authors.lastname: Ginestier
authors.forename: Florence
authors.initials: F
authors.lastname: Monville
authors.forename: Séverine
authors.initials: S
authors.lastname: Esteyriès
authors.forename: José
authors.initials: J
authors.lastname: Adélaïde
authors.forename: Benjamin
authors.initials: B
authors.lastname: Esterni
authors.forename: Catherine
authors.initials: C
authors.lastname: Henry
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Ethier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bibeau
authors.forename: Marie-Joëlle
authors.initials: MJ
authors.lastname: Mozziconacci
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Charles
authors.initials: C
authors.lastname: Theillet
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000235:genetics*; D016615:Telomere / Q000235:genetics; D046888:Tissue Array Analysis