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Nature Genetics  12, 333 - 337 (1996)

The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds

S.V. Tavtigian1, J. Simard2, J. Rommens3, F. Couch4, D. Shattuck-Eidens1, S. Neuhausen5, S. Merajver6, S. Thorlacius7, K. Offit8, D. Stoppa-Lyonnet9, C. Belanger2, R. Bell1, S. Berry1, R. Bogden1, Q. Chen1, T. Davis1, M. Dumont2, C. Frye1, T. Hattier1, S. Jammulapati1, T. Janecki1, P. Jiang1, R. Kehrer1, J.-F. Leblanc2, J.T. Mitchell1, J. McArthur-Morrison3, K. Nguyen5, Y. Peng4, C. Samson2, M. Schroeder1, S.C. Snyder3, L. Steele5, M. Stringfellow1, C. Stroup1, B. Swedlund1, J. Swense5, D. Teng1, A. Thomas1, T. Tran5, M. Tranchant2, J. Weaver-Feldhaus1, A.K.C. Wong1, H. Shizuya10, J.E. Eyfjord7, L. Cannon-Albright5, M. Tranchant2, F. Labrie2, M.H. Skolnick1, 5, B. Weber4, A. Kamb1 & D.E. Goldgar5, 11

  1Myriad Genetics Inc., Salt Lake City, Utah USA.

  2Laboratory of Molecular Endocrinology, CHUL Research Center and Laval University, Quebec City, Canada.

  3Department of Genetics, Hospital for Sick Children, University of Toronto, Ontario, Canada.

  4Deparment of Hematology-Oncology, University of Pennsylvania, Philadelphia, USA.

  5Genetic Epidemiology Group, Department of Medical Informatics and Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA

  6 Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.

  7Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Rekjavik, Iceland.

  8Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

  9Unite de Genetique Oncologique, Institute Curie, Paris, France.

  10Division of Biology, California Institute of Technology, Pasadena, California, USA.

  11Unit of Genetic Epidemiology, International Agency for Research on Cancer, 150 cours Albert Thomas, 63972, Lyon, Cedex08, France.

 Correspondence should be addressed to D.E.G.

Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds1. BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds2, and then identified four years later by a positional cloning strategy3. BRCA2 was mapped to chromosomal 13q at about the same time4. Just fifteen months later, Wooster et al.5 reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession sharpU43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DMA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.

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