Nature Genetics
13, 123 - 125 (1996)
doi:10.1038/ng0596-123
BRCA2 germline mutations in male breast cancer cases and breast cancer familiesFergus J. Couch1, Linda M. Farid2, Michelle L. DeShano1, Sean V. Tavtigian3, Kathleen Calzone1, Lisa Campeau1, Yi Peng1, Bert Bogden3, Qian Chen3, Susan Neuhausen4, Donna Shattuck-Eidens3, Andrew K. Godwin5, Mary Daly5, Diane M. Radford6, Scott Sedlacek7, Johanna Rommens8, Jacques Simard9, Judy Garber10, Sofia Merajver11
& Barbara L. Weber1, 12, 13
1Dept of Medicine, 1010 Stellar Chance Laboratories, 422 Curie Boulevard, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
2Dept of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
3Myriad Genetics Inc., Salt Lake City, Utah 84108, USA.
4Dept of Genetic Epidemiology, University of Utah, Salt Lake City, Utah 84108, USA
5Dept of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
6Dept of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA
7Dept of Medicine, University of Colorado, Denver, Colorado 80220, USA
8Dept of Genetics, Hospital for Sick Children, Toronto M5G1X8, Canada
9Dept of Molecular Endocrinology, CHUL Research Center and Laval University, Quebec City GIV4G2, Canada
10Division of Cancer Epidemiology and Control, Dana Farber Cancer Institute, Boston, Massachusettes 02115, USA
11Dept of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
12Dept of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
13Correspondence should be addressed to B.L.W. The breast cancer susceptibility gene, BRCA2 on chromosome 13q12−13, was recently isolated1−3. Mutations in BRCA2 are thought to account for as much as 35% of all inherited breast cancer as well as a proportion of inherited ovarian cancer1. Many BRC2-linked families also contain cases of male breast cancer. We have analysed germline DMA from 50 males with breast cancer (unselected for family history) and 26 individuals from site-specific female breast and breast−ovarian cancer families for mutations in BRCA2. All 17 breast−ovarian cancer families have been screened for BRCA1 coding region mutations and none were detected. Conformation-sensitive gel electrophoresis (CSGE) analysis of PCR-amplifed DMA followed by direct sequencing was used to detect sequence variants. Three of eleven individuals carry the same mutation, all are of Ashkenazi Jewish descent, supporting the observation by Neuhausen et al, in this issue4 that there is a common mutation in this population. Eleven truncating mutations and nine polymorphisms were identified — all were coding region variants. No loss-of-transcript mutations were identified in the sixteen samples for which this analysis was possible. Seven of the nine disease-associated mutations were detected in the 50 men with breast cancers; thus in our series, BRCA2 mutations account for 14% of male breast cancer, all but one of which had a family history of male and/or female breast cancer.
REFERENCES
- Wooster, R. et al. Localisation of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12−13. Science 285, 2088−2090 (1994).
- Wooster, R. et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 378, 789−792 (1995). | Article | PubMed | ISI | ChemPort |
- Tavtigian, S.V. et al. The complete BRCA2 gene and mutations in chromsome 13q-linked kindreds. Nature Genet. 12, 333−337 (1996). | Article | PubMed | ISI | ChemPort |
- Neuhausen, S. et al. Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer. Nature Genet. 13, 126−128 (1996). | Article | PubMed | ISI | ChemPort |
- Ganguly, A., Rock, M.J. & Prockop, D.J. Conformation-sensitive gel electrophoresis for rapid detection of single base differences in double stranded PCR products and DNA fragments: evidence for solvent induced bends in DNA heteroduplexes. Proc. Natl. Acad. Sci. USA 86, 2766−70 (1989). | PubMed | ChemPort |
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