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Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer

Nature Genetics volume 8, pages 387–391 (1994)Cite this article

Abstract

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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Authors and Affiliations

  1. National Center for Human Genome Research, National Institutes of Health, Building 49/3A14, Bethesda, Maryland, 20892, USA

    Lucio H. Castilla, Michael R. Erdos, Lawrence C. Brody & Francis S. Collins

  2. Department of Biology, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Lucio H. Castilla

  3. Department of Internal Medicine, University of Pennsylvania, 1010 BRBI, 422 Curie Boulevard, Philadelphia, Pennsylvania, 19104, USA

    Fergus J. Couch, Kent F. Hoskins, Kathy Calzone, Michelle L. Deshano & Barbara L. Weber

  4. Division of Cancer Epidemiology and Control, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts, 02115, USA

    Judy E. Garber

  5. Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Jeff Boyd

  6. Strang Cancer Prevention Center, 428 East 72nd Street, New York, New York, 10021, USA

    Matthew B. Lubin

  7. Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Barbara L. Weber

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  1. Lucio H. Castilla
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Castilla, L., Couch, F., Erdos, M. et al. Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer. Nat Genet 8, 387–391 (1994). https://doi.org/10.1038/ng1294-387

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  • DOI: https://doi.org/10.1038/ng1294-387

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