Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families (original) (raw)

Nature Genetics volume 8, pages 392–398 (1994)Cite this article

Abstract

Women who carry mutations in the BRCA1 gene on chromosome 17q have an 85% lifetime risk of breast cancer, and a 60% risk of ovarian cancer. We have identified BRCA1 mutations in 12 of 30 (40%) Canadian families with breast and/or ovarian cancer, including six of the eight families (75%) that contained two cases of early-onset breast cancer and two cases of ovarian cancer. Six frameshift mutations account for all 12 mutant alleles, including nucleotide insertions (two mutations) and deletions (four mutations). Four independent families carried the same 1 basepair (bp) insertion mutation in codon 1755 and four other families shared a 2 bp deletion mutation in codons 22–23. These families were not known to be related, but haplotype analysis suggests that the carriers of each of these mutations have common ancestors.

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Authors and Affiliations

  1. Laboratory of Molecular Endocrinology, CHUL Research Center and Laval University, 2705, boul. Laurier, Quebec City, Quebec, G1V 4G2, Canada
    J. Simard, F. Durocher, S. Gingras, C. Samson, J.-F. Leblanc, C. Bélanger & F. Labrie
  2. Division of Medical Genetics, Department of Medicine and Department of Human Genetics, McGill University, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada
    P. Tonin, K. Morgan, F. Dion & S.A. Narod
  3. Department of Epidemiology and Biostatistics, McGill University, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada
    K. Morgan
  4. Department of Genetics, Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada
    J. Rommens
  5. Myriad Genetics Inc., Salt Lake City, Utah, USA
    Q. Liu, M. Skolnick & D. Shattuck-Eidens
  6. Department of Medical Informatics, University of Utah, Salt Lake City, Utah, USA
    M. Skolnick & D. Goldgar

Authors

  1. J. Simard
  2. P. Tonin
  3. F. Durocher
  4. K. Morgan
  5. J. Rommens
  6. S. Gingras
  7. C. Samson
  8. J.-F. Leblanc
  9. C. Bélanger
  10. F. Dion
  11. Q. Liu
  12. M. Skolnick
  13. D. Goldgar
  14. D. Shattuck-Eidens
  15. F. Labrie
  16. S.A. Narod

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Simard, J., Tonin, P., Durocher, F. et al. Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families.Nat Genet 8, 392–398 (1994). https://doi.org/10.1038/ng1294-392

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