Nature Genetics
13, 241 - 244 (1996)
doi:10.1038/ng0696-241
Low incidence of BRCA2 mutations in breast carcinoma and other cancersDavid H.-R Teng1, Robert Bogden1, Jeffrey Mitchell1, Michelle Baumgard1, Russell Bell1, Simin Berry1, Thaylon Davis1, Phuong C. Ha1, Robert Kehrer1, Srikanth Jammulapati1, Qian Chen1, Kenneth Offit2, Mark H. Skolnick1, Sean V. Tavtigian1, Suresh Jhanwar2, Brad Swedlund1, Alexander K.C. Wong1, 3
& Alexander Kamb1
1Myriad Genetics, Inc., Wakara Way, Salt Lake City, Utah 84108, USA
2Departmentof Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NewYork 10021, USA
3e-mail:akamb@myriad.com Inherited mutant alleles of familial tumour suppressor genes predispose individuals to particular types of cancer. In addition to an involvement in inherited susceptibility to cancer, these tumour suppressor genes are targets for somatic mutations in sporadic cancers of the same type found in the familial forms1. An exception is BRCA1, which contributes to a significant fraction of familial breast and ovarian cancer, but undergoes mutation at very low rates in sporadic breast and ovarian cancers2−4. This finding suggests that other genes may be the principal targets for somatic mutation in breast carcinoma. A second, recently identified familial breast cancer gene, BRCA2 (refs 5−8), accounts for a proportion of breast cancer roughly equal to BRCA1. Like BRCA1, BRCA2 behaves as a dominantly inherited tumour suppressor gene. Individuals who inherit one mutant allele are at increased risk for breast cancer, and the tumours they develop lose the wild-type allele by heterozygous deletion9. The BRCA2 coding sequence is huge, composed of 26 exons that span 10,443 bp8. Here we investigate the rate of BRCA2 mutation in sporadic breast cancers and in a set of cell lines that represent twelve other tumour types. Surprisingly, mutations in BRCA2 are infrequent in cancers including breast carcinoma. However, a probable germline mutation in a pancreatic tumour cell line suggests a role for BRCA2 in susceptibility to pancreatic cancer.
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