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Large genomic rearrangements of both BRCA2 and BRCA1 are a feature of the inherited breast/ovarian cancer phenotype in selected families
  1. A M Woodward1,
  2. T A Davis1,
  3. A G S Silva1,
  4. kConFab Investigators2,
  5. J A Kirk1,
  6. J A Leary1
  1. 1Familial Cancer Service, Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia
  2. 2Kathleen Cuningham Consortium for Research into Familial Breast Cancer, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002, Australia
  1. Correspondence to:
 Jennifer Leary
 Familial Cancer Service, Westmead Hospital, Westmead, NSW 2145, Australia;


Introduction: 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.

Conclusion: 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).

  • MLPA, multiplex ligation dependent probe amplification
  • BRCA1
  • BRCA2
  • inherited breast/ovarian cancer
  • large genomic rearrangements

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  • Supported by the University of Sydney Cancer Research Fund, the Western Sydney Area Health Service, Perpetual Philanthropic Foundations NSW. kConFab is supported by the National Breast Cancer Foundation, the National Health and Medical Research Council, and the State Cancer Councils of Australia.

  • Competing interests: none declared

  • Accession numbers ( BRCA1: U14680.1, L78833.1, AAA73985.1; BRCA2: U43746.1, Z74739.1, AAB07223.1.

  • Ethics approval for this study has been granted by the Western Sydney Area Health Service Human Research Ethics Committee and the University of Sydney Human Ethics Committee.