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Letters to Nature

Nature 378, 789-792 (28 December 1995) | doi:10.1038/378789a0; Accepted 7 December 1995

Identification of the breast cancer susceptibility gene BRCA2

Richard Wooster*, Graham Bignell*, Jonathan Lancaster‡, Sally Swift†, Sheila Seal*, Jonathan Mangion*, Nadine Collins*, Simon Gregory§, Curtis Gumbsparallel, Gos Micklem§, Rita Barfoot*, Rifat Hamoudi*, Sandeep Patel*, Catherine Rices§, Patrick Biggs*, Yasmin Hashim*, Amanda Smith†, Frances Connor†, Adalgeir Arason, Julius Gudmundsson, David Ficenec¶***, David Kelsell£, Deborah Fordstar, Patricia Tonin**, D. Timothy Bishop††, Nigel K. Spurr£, Bruce A. J. Ponder‡‡, Rosalind Eeles*, Julian Petostar, Peter Devilee§§, Cees Cornelisse§§, Henry Lynchparallelparallel, Steven Narod**starstar, Gilbert Lenoir¶¶, Valdgardur Egilsson, Rosa Bjork Barkadottir, Douglas F. Easton££, David R. Bentley§, P. Andrew Futrealparallel, Alan Ashworth† & Michael R. Stratton*

  1. Sections of *,  Molecular Carcinogenesis and star,  Epidemiology, and † CRC Centre for Cell and Molecular Biology, Institute of Cancer Research, Haddow Laboratories, 15 Cotswold Road, Button, Surrey SM2 5NG, UK, and Chester Beatty Laboratories, Fulham Road, London SW3 6JB, UK
  2. ‡ Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
  3. § The Sanger Centre, Hinxton Hall, Hinxton, Cambridgeshire CB10 IRQ, UK
  4. parallel Duke University Medical Centre, Departments of Surgery and Genetics, and Division of Gynaecologic Oncology, Research Drive, Medical Sciences Research Building, Room 363, Durham, North Carolina 27710, USA
  5. Laboratory of Cell Biology, University Hospital of Iceland, P.O. Box 1465, IS-121 Reykjavik, Iceland
  6. £ ICRF Clare Hall Laboratories, Blanche Lane, South Mimms, Potters Bar EN6 3LD, UK
  7. ** Division of Medical Genetics and Division of Human Genetics, Dept of Medicine, McGill University, 1650 Cedar Avenue, Montreal, H3G 1A4, Canada
  8. †† ICRF Genetic Epidemiology Laboratory, 3K Springfield House, Hyde Terrace, Leeds LS2 9LU, UK
  9. ‡‡ CRC Human Cancer Genetics Research Group, Level 3, Laboratories Block, Box 238, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ, UK
  10. §§ Department of Human Genetics and Pathology, Leiden University, Wassenaarseweg 72, P. 0. Box 9503, 2300 RA, Leiden, The Netherlands
  11. parallelparallel Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska 68178, USA
  12. ¶¶ International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France
  13. ££ CRC Genetic Epidemiology Group, Department of Community Medicine, Institute of Public Health, University of Cambridge, University Forvie Site, Robinson Way, Cambridge CB2 2SR, UK
  14. starstar Women's College Hospital, Toronto, Ontario, Canada
  15. *** Genome Sequencing Centre, Washington University in St Louis, School of Medicine, St Louis, MO, USA
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IN Western Europe and the United States approximately 1 in 12 women develop breast cancer. A small proportion of breast cancer cases, in particular those arising at a young age, are attributable to a highly penetrant, autosomal dominant predisposition to the disease. The breast cancer susceptibility gene, BRCA2, was recently localized to chromosome 13q12-q13. Here we report the identification of a gene in which we have detected six different germline mutations in breast cancer families that are likely to be due to BRCA2. Each mutation causes serious disruption to the open reading frame of the transcriptional unit. The results indicate that this is the BRCA2 gene.