High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes

• Published in: PloS one 2011-02, Vol.6 (2), p.e16950-e16950
• Main Authors: Bekhouche, Ismahane, Finetti, Pascal, Adelaïde, José, Ferrari, Anthony, Tarpin, Carole, Charafe-Jauffret, Emmanuelle, Charpin, Colette, Houvenaeghel, Gilles, Jacquemier, Jocelyne, Bidaut, Ghislain, Birnbaum, Daniel, Viens, Patrice, Chaffanet, Max, Bertucci, François
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adult; Aged; Aged, 80 and over; Biology; Breast cancer; Cancer; Cancer genetics; Cell cycle; Cell growth; Cell migration; Chromosome Aberrations; Comparative analysis; Comparative Genomic Hybridization - methods; Copy number; Cytogenetics; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA microarrays; Extracellular matrix; Female; Fibroblasts; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genetic Association Studies - methods; Genomes; Genomic instability; Genomics; High resolution; Humans; Hybridization; Inflammation; Inflammatory Breast Neoplasms - genetics; Invasiveness; Life Sciences; Medical prognosis; Medical research; Medicine; Metabolism; Metastasis; Microarray Analysis; Middle Aged; Oncology; Phosphatase; Prostate cancer; Proteins; Ribonucleic acid; RNA; RNA processing; Stability; Studies; Transcription; Transcription (Genetics); Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0016950

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. 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. 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.