title: Large genomic rearrangements of both BRCA2 and BRCA1 are a feature of the inherited breast/ovarian cancer phenotype in selected families.
abstract: BACKGROUND
  A strong family history of breast and/or ovarian cancer can often be explained by small insertions, deletions, or substitutions in BRCA1 or BRCA2 and large genomic rearrangements in BRCA1. However, there is little evidence that genomic rearrangements are a major factor in BRCA2 associated breast cancer and the frequencies of rearrangements in BRCA1 in large clinic based populations are unknown.
  
  
  OBJECTIVE
  To investigate the frequency of large genomic rearrangements in BRCA1 and BRCA2 in a large clinic based population at high risk of developing breast and/or ovarian cancer.
  
  
  METHODS
  Multiplex ligation dependent probe amplification was used to comprehensively screen BRCA1 and/or BRCA2 in 312 index cases.
  
  
  RESULTS
  Three novel deletions detected in BRCA2 were found exclusively in families with at least one case of male breast cancer. Novel rearrangements in BRCA1 were detected mostly in families with both breast and ovarian cancer. Families with these mutations were significantly younger at average age of cancer diagnosis.
  
  
  CONCLUSIONS
  Screening for large genomic rearrangements in both BRCA1 and BRCA2 is strongly supported by this study, in particular in multiple case breast/ovarian families with a young age of onset (BRCA1) and families containing at least one case of male breast cancer (BRCA2).
authors.affiliation: Familial Cancer Service, Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Woodward
authors.forename: T A
authors.initials: TA
authors.lastname: Davis
authors.forename: A G S
authors.initials: AG
authors.lastname: Silva
authors.forename: J A
authors.initials: JA
authors.lastname: Kirk
authors.forename: J A
authors.initials: JA
authors.lastname: Leary
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D002869:Chromosome Aberrations; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype