Large genomic rearrangements of the BRCA1 and BRCA2 genes: review of the literature and report of a novel BRCA1 mutation
Open Access
- 16 March 2010
- journal article
- review article
- Published by Springer Science and Business Media LLC in Breast Cancer Research and Treatment
- Vol. 125 (2), 325-349
- https://doi.org/10.1007/s10549-010-0817-z
Abstract
Germline mutations in BRCA1 and BRCA2 increase the risk for developing breast and ovarian cancer. Previously, the techniques available allowed only for the identification of small genomic alterations, but the dawn of new technology now allows for the rapid detection of large genomic rearrangements (LGRs). LGRs in BRCA1 are responsible for between 0 and 27% of all BRCA1 disease-causing mutations identified in numerous populations. Such alterations are far less common in the BRCA2 gene. To determine the impact of BRCA1 and BRCA2 LGRs in South Africa, 52 hereditary breast and/or ovarian South African families (36 were Afrikaners) were screened for BRCA1 and BRCA2 LGRs using multiplex ligation-dependent probe amplification. These patients were previously shown to be BRCA1 and BRCA2 small mutation negative. One LGR was detected in BRCA1 in a South African family with Greek ancestry. This is a novel deletion of both exons 23 and 24 (NG_005905.2:g.169527_180579del). This first study of BRCA rearrangements in South Africa reveals that LGRs comprise ~3% of identified BRCA1 mutations, a low rate in comparison to other populations. In addition, we have reviewed all 98 previously characterized BRCA1/2 LGRs and re-named them according to the recommended HGVS nomenclature, using the recently released RefSeqGene records, NG_005905.2 and NG_012772.1 for BRCA1 and BRCA2. A standardized resource is now provided which will assist researchers in determining whether their LGRs are novel. Furthermore, we have clarified some of the previously misunderstood rules of nomenclature, which will make uniform reporting of BRCA1/2 easier in the future.This publication has 82 references indexed in Scilit:
- Screening for a BRCA2 Rearrangement in High-Risk Breast/Ovarian Cancer Families: Evidence for a Founder Effect and Analysis of the Associated PhenotypesJournal of Clinical Oncology, 2007
- The contribution of germline rearrangements to the spectrum of BRCA2 mutationsJournal of Medical Genetics, 2006
- Large genomic deletions inactivate the BRCA2 gene in breast cancer familiesJournal of Medical Genetics, 2005
- Significant Contribution of Germline BRCA2 Rearrangements in Male Breast Cancer FamiliesCancer Research, 2004
- Dosage analysis of cancer predisposition genes by multiplex ligation-dependent probe amplificationBritish Journal of Cancer, 2004
- Genetic Heterogeneity and Penetrance Analysis of the BRCA1 and BRCA2 Genes in Breast Cancer FamiliesAmerican Journal of Human Genetics, 1998
- Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1.Genome Research, 1996
- Identification of the breast cancer susceptibility gene BRCA2Nature, 1995
- The genetics of breast and ovarian cancerBritish Journal of Cancer, 1995
- A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1Science, 1994