title: Large genomic deletions inactivate the BRCA2 gene in breast cancer families.
abstract: BACKGROUND
  BRCA1 and BRCA2 are the two major genes responsible for the breast and ovarian cancers that cluster in families with a genetically determined predisposition. However, regardless of the mutation detection method employed, the percentage of families without identifiable alterations of these genes exceeds 50%, even when applying stringent criteria for family selection. A small but significant increase in mutation detection rate has resulted from the discovery of large genomic alterations in BRCA1. A few studies have addressed the question of whether BRCA2 might be inactivated by the same kinds of alteration, but most were either done on a relatively small number of samples or employed cumbersome mutation detection methods of variable sensitivity.
  
  
  OBJECTIVE
  To analyse 121 highly selected families using the recently available BRCA2 multiplex ligation dependent probe amplification (MLPA) technique.
  
  
  RESULTS
  Three different large genomic deletions were identified and confirmed by analysis of the mutant transcript and genomic characterisation of the breakpoints.
  
  
  CONCLUSIONS
  Contrary to initial suggestions, the presence of BRCA2 genomic rearrangements is worth investigating in high risk breast or ovarian cancer families.
authors.affiliation: Department of Oncology and Surgical Sciences, Oncology Section, Padua, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Agata
authors.forename: M
authors.initials: M
authors.lastname: Dalla Palma
authors.forename: M
authors.initials: M
authors.lastname: Callegaro
authors.forename: M C
authors.initials: MC
authors.lastname: Scaini
authors.forename: C
authors.initials: C
authors.lastname: Menin
authors.forename: C
authors.initials: C
authors.lastname: Ghiotto
authors.forename: O
authors.initials: O
authors.lastname: Nicoletto
authors.forename: G
authors.initials: G
authors.lastname: Zavagno
authors.forename: L
authors.initials: L
authors.lastname: Chieco-Bianchi
authors.forename: E
authors.initials: E
authors.lastname: D'Andrea
authors.forename: M
authors.initials: M
authors.lastname: Montagna
mesh_terms: D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D016678:Genome; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011995:Recombination, Genetic
chemical_list: D024682:BRCA2 Protein