Nature Genetics
8, 387 - 391 (1994)
doi:10.1038/ng1294-387
Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancerLucio H. Castilla1, 2, *, Fergus J. Couch3, *, Michael R. Erdos1, *, Kent F. Hoskins3, Kathy Calzone3, Judy E. Garber4, Jeff Boyd5, Matthew B. Lubin6, Michelle L. Deshano3, Lawrence C. Brody1, Francis S. Collins1
& Barbara L. Weber3, 7, 8
1National Center for Human Genome Research, Building 49/3A14, National Institutes of Health, Bethesda, Maryland 20892, USA
2Department of Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
3Department of Internal Medicine, 1010 BRBI, 422 Curie Boulevard, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
4Division of Cancer Epidemiology and Control, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
5Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
6Strang Cancer Prevention Center, 428 East 72nd Street, New York, New York 10021, USA
7Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
8Correspondence should be addressed to B.L.W. We analysed 50 probands with a family history of breast and/or ovarian cancer for germline mutations in the coding region of the BRCA1 candidate gene, using single-strand conformation polymorphism (SSCP) analysis on PCR-amplified genomic DNA. A total of eight putative disease-causing alterations were identified: four of these are frameshifts and two are nonsense mutations. In addition, we found two missense mutations, one of which changes the final cysteine of the BRCA1 zinc finger motif to glycine. These data are consistent with a tumour suppressor model, and support the notion that this candidate gene is in fact BRCA1. The heterogeneity of mutations, coupled with the large size of the gene, indicates that clinical application of BRCA1 mutation testing will be technically challenging.
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