title: High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.
abstract: BACKGROUND
  Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples.
  
  
  RESULTS
  Genomic imbalances of 49 IBCs and 124 nIBCs were determined using high-resolution array-comparative genomic hybridization, and mRNA expression profiles of 197 samples using whole-genome microarrays. Genomic profiles of IBCs were as heterogeneous as those of nIBCs, and globally relatively close. However, IBCs showed more frequent "complex" patterns and a higher percentage of genes with CNAs per sample. The number of altered regions was similar in both types, although some regions were altered more frequently and/or with higher amplitude in IBCs. Many genes were similarly altered in both types; however, more genes displayed recurrent amplifications in IBCs. The percentage of genes whose mRNA expression correlated with CNAs was similar in both types for the gained genes, but ∼7-fold lower in IBCs for the lost genes. Integrated analysis identified 24 potential candidate IBC-specific genes. Their combined expression accurately distinguished IBCs and nIBCS in an independent validation set, and retained an independent prognostic value in a series of 1,781 nIBCs, reinforcing the hypothesis for a link with IBC aggressiveness. Consistent with the hyperproliferative and invasive phenotype of IBC these genes are notably involved in protein translation, cell cycle, RNA processing and transcription, metabolism, and cell migration.
  
  
  CONCLUSIONS
  Our results suggest a higher genomic instability of IBC. We established the first repertory of DNA copy number alterations in this tumor, and provided a list of genes that may contribute to its aggressiveness and represent novel therapeutic targets.
authors.affiliation: Marseille Cancer Research Center (CRCM), UMR891 Inserm, Institut Paoli-Calmettes, Department of Molecular Oncology, Marseille, France.
authors.forename: Ismahane
authors.initials: I
authors.lastname: Bekhouche
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: José
authors.initials: J
authors.lastname: Adelaïde
authors.forename: Anthony
authors.initials: A
authors.lastname: Ferrari
authors.forename: Carole
authors.initials: C
authors.lastname: Tarpin
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.forename: Colette
authors.initials: C
authors.lastname: Charpin
authors.forename: Gilles
authors.initials: G
authors.lastname: Houvenaeghel
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Ghislain
authors.initials: G
authors.lastname: Bidaut
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000235:genetics*; D046228:Microarray Analysis; D008875:Middle Aged; D055815:Young Adult