title: Deletion of chromosomes 13q and 14q is a common feature of tumors with BRCA2 mutations.
abstract: BACKGROUND
  Germline BRCA1 or BRCA2 mutations account for 20-30% of familial clustering of breast cancer. The main indication for BRCA2 screening is currently the family history but the yield of mutations identified in patients selected this way is low.
  
  
  METHODS
  To develop more efficient approaches to screening we have compared the gene expression and genomic profiles of BRCA2-mutant breast tumors with those of breast tumors lacking BRCA1 or BRCA2 mutations.
  
  
  RESULTS
  We identified a group of 66 genes showing differential expression in our training set of 7 BRCA2-mutant tumors and in an independent validation set of 19 BRCA2-mutant tumors. The differentially expressed genes include a prominent cluster of genes from chromosomes 13 and 14 whose expression is reduced. Gene set enrichment analysis confirmed that genes in specific bands on 13q and 14q showed significantly reduced expression, suggesting that the affected bands may be preferentially deleted in BRCA2-mutant tumors. Genomic profiling showed that the BRCA2-mutant tumors indeed harbor deletions on chromosomes 13q and 14q. To exploit this information we have created a simple fluorescence in situ hybridization (FISH) test and shown that it detects tumors with deletions on chromosomes 13q and 14q.
  
  
  CONCLUSIONS
  Together with previous reports, this establishes that deletions on chromosomes 13q and 14q are a hallmark of BRCA2-mutant tumors. We propose that FISH to detect these deletions would be an efficient and cost-effective first screening step to identify potential BRCA2-mutation carriers among breast cancer patients without a family history of breast cancer.
authors.affiliation: French National Institute of Health and Medical Research (INSERM) Unit 916, University of Bordeaux, Bergonié Cancer Institute, Bordeaux, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Rouault
authors.forename: Guillaume
authors.initials: G
authors.lastname: Banneau
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Macgrogan
authors.forename: Natalie
authors.initials: N
authors.lastname: Jones
authors.forename: Nabila
authors.initials: N
authors.lastname: Elarouci
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Barouk-Simonet
authors.forename: Laurence
authors.initials: L
authors.lastname: Venat
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coupier
authors.forename: Eric
authors.initials: E
authors.lastname: Letouzé
authors.forename: Aurélien
authors.initials: A
authors.lastname: de Reyniès
authors.forename: Françoise
authors.initials: F
authors.lastname: Bonnet
authors.forename: Richard
authors.initials: R
authors.lastname: Iggo
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sévenet
authors.forename: Michel
authors.initials: M
authors.lastname: Longy
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D002883:Chromosomes, Human, Pair 14; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D015203:Reproducibility of Results