Rapid detection of BRCA1 mutations by the protein truncation test (original) (raw)

Nature Genetics volume 10, pages 208–212 (1995)Cite this article

Abstract

More than 75% of the reported mutations in the hereditary breast and ovarian cancer gene, BRCA1, result in truncated proteins. We have used the protein truncation test (PIT) to screen for mutations in exon 11, which encodes 61 % of BRCA1. In 45 patients from breast and/or ovarian cancer families we found six novel mutations: two single nucleotide insertions, three small deletions (1–5 bp) and a nonsense mutation identified two unrelated families. Furthermore, we were able to amplify the remaining coding region by RT–PCR using lymphocyte RNA. Combined with PTT, we detected aberrantly spliced products affecting exons 5 and 6 in one of two _BRCA1_–linked families examined. The protein truncation test promises to become a valuable technique in detecting BRCA1 mutations.

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Authors and Affiliations

  1. MGC-Department of Human Genetics, University of Leiden, Wassenaarseweg 72, Leiden, 2333 AL, The Netherlands
    Frans B.L. Hogervorst, Renée S. Cornelis, Mattie Bout, Margreethe van Vliet, Johan T. den Dunnen, Peter Devilee & Gert-Jan B. van Ommen
  2. Department of Clinical Genetics, University Hospital, Rijnsburgerweg 10, Leiden, 2333 AA, The Netherlands
    Jan C. Oosterwijk, Renske Olmer & Bert Bakker
  3. Daniël den Hoed Hospital, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands
    Jan G.M. Klijn
  4. Foundation for the Detection of Hereditary Tumours, Rijnsburgerweg 10, 2333 AA, Leiden, The Netherlands
    Hans F.A. Vasen
  5. Department of Clinical Genetics, Erasmus University, Dr. Molewaterplein 50, Rotterdam, 3015 GE, The Netherlands
    Hanna Meijers-Heijboer
  6. Department of Clinical Genetics, Free University Hospital, Boelenlaan 1117, Amsterdam, 1081 HV, The Netherlands
    Fred H. Menko
  7. Department of Pathology, University of Leiden, Wassenaarseweg 72, Leiden, 2333 AL, The Netherlands
    Cees J. Cornelisse & Peter Devilee

Authors

  1. Frans B.L. Hogervorst
  2. Renée S. Cornelis
  3. Mattie Bout
  4. Margreethe van Vliet
  5. Jan C. Oosterwijk
  6. Renske Olmer
  7. Bert Bakker
  8. Jan G.M. Klijn
  9. Hans F.A. Vasen
  10. Hanna Meijers-Heijboer
  11. Fred H. Menko
  12. Cees J. Cornelisse
  13. Johan T. den Dunnen
  14. Peter Devilee
  15. Gert-Jan B. van Ommen

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Hogervorst, F., Cornelis, R., Bout, M. et al. Rapid detection of BRCA1 mutations by the protein truncation test.Nat Genet 10, 208–212 (1995). https://doi.org/10.1038/ng0695-208

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