Nature Genetics
10, 208 - 212 (1995)
doi:10.1038/ng0695-208
Rapid detection of BRCA1 mutations by the protein truncation testFrans B.L. Hogervorst1, Renée S. Cornelis1, Mattie Bout1, Margreethe van Vliet1, Jan C. Oosterwijk2, Renske Olmer2, Bert Bakker2, Jan G.M. Klijn3, Hans F.A. Vasen4, Hanna Meijers-Heijboer5, Fred H. Menko6, Cees J. Cornelisse7, Johan T. den Dunnen1, Peter Devilee1, 7
& Gert-Jan B. van Ommen1
1MGC-Department of Human Genetics, University of Leiden, Wassenaarseweg 72, 2333 AL, Leiden, The Netherlands
2Department of Clinical Genetics, University Hospital, Rijnsburgerweg 10, 2333 AA, Leiden, The Netherlands
3Daniël den Hoed Hospital, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands
4Foundation for the Detection of Hereditary Tumours, Rijnsburgerweg 10, 2333 AA, Leiden, The Netherlands
5Department of Clinical Genetics, Erasmus University, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
6Department of Clinical Genetics, Free University Hospital, Boelenlaan 1117, 1081 HV, Amsterdam, The Netherlands
7Department of Pathology, University of Leiden, Wassenaarseweg 72, 2333 AL, Leiden, The Netherlands Correspondence should be addressed to F.B.L.H. 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.
REFERENCES
- Hall, J. et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250, 1684–1689 (1990). | PubMed | ISI | ChemPort |
- Wooster, R. et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12–13. Science 265, 2088–2090 (1994). | PubMed | ISI | ChemPort |
- Easton, D.F. et al. Genetic linkage analysis in familial breast and ovarian cancer: Results from 214 families. Am. J. hum. Genet. 52, 678–701 (1993). | PubMed | ISI | ChemPort |
- Ford, D. et al. Risks of cancer in BRCA1-mutation carriers. Lancet 343, 692–695 (1994). | Article | PubMed | ISI | ChemPort |
- Miki, Y. et al. Astrong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266, 66–71 (1994). | PubMed | ISI | ChemPort |
- Lynch, H.T. et al. Genetic epidemiology of cancer (eds Lynch, H.T. & Hirayama, T.) 289–332 (CRC Press, Boca Baton, 1989).
- Nowak, R. Breast cancer gene: many mutations make test difficult. Science 266, 1470 (1994). | PubMed | ISI | ChemPort |
- Castilla et al. Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer. Nature Genet. 8, 387–391 (1994). | Article | PubMed | ISI | ChemPort |
- Futreal, P.A. et al. BRCA1 mutations in primary breast and ovarian carcinomas. Science 266, 120–122 (1994). | PubMed | ISI | ChemPort |
- Simard, J. et al. Common origin of BRCA1 mutations in Canadian breast and ovarian cancer families. Nature Genet. 8, 392–398 (1994). | Article | PubMed | ISI | ChemPort |
- Friedman, L.S. et al. Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families. Nature Genet. 8, 399–404 (1994). | Article | PubMed | ISI | ChemPort |
- Shuttuck-Eidens, D. et al. A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. J. Am. med. Assoc. 273, 535–541 (1995). | Article |
- Roest, P.A.M., Roberts, R.G., Sugino, S., Van Ommen, G.J.B. & Den Dunnen, J.T. Protein truncation test (PTT) for rapid detection of translation-terminating mutations. Hum. molec. Genet. 2, 1719–1721 (1993). | PubMed | ISI | ChemPort |
- Van Der Luit, R. et al. Rapid detection of translation-terminating mutations at the Adenomatous Polyposis Coli (APC) gene by direct Protein Truncation Test. Genomics 20, 1–4 (1994). | Article | PubMed |
- Powell, S.M. et al. Molecular diagnosis of Familial Adenomatous Polyposis. New Engl. J. Med. 329, 1982–1987 (1993). | Article | PubMed | ISI | ChemPort |
- Roberts, R.G., Barby, T.F.M., Manners, E., Bobrow, M. & Bently, D.R. Direct detection of dystrophin gene rearrangements by analysis of dystrophin mRNA in peripheral blood lymphocytes. Am. J. hum. Genet. 49, 298–310 (1991). | PubMed | ISI | ChemPort |
- Narod, S.A. et al. A number of breast-ovarian cancer families appear to be unlinked to the BRCA1 locus on chromosome 17q. Am. J. hum. Genet. 56, 254–264 (1995). | PubMed | ISI | ChemPort |
- Comelis, R.S. et al. Age at diagnosis as an indicator of eligibility for BRCA1 DNA-testing in familial breast cancer. Hum. Genet. 119, (in the press).
- Miller, S.A., Dykes, D.D. & Polesky, H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nud. Acids Res. 16, 1215 (1988). | ChemPort |
|
