BRCA2 founder mutation in Slovenian breast cancer families (original) (raw)

European Journal of Human Genetics volume 10, pages 879–882 (2002)Cite this article

Abstract

Linkage analysis has identified BRCA1 and BRCA2 germline mutations as the major cause for cancer predisposition in breast and/or ovarian cancer families. In previous screening efforts on Belgian families we had a BRCA1/2 gene mutation detection rate of 25%.1 Here we report the results of a BRCA mutation screening in seven high-risk breast/ovarian cancer families from Slovenia. We found a single but highly recurrent BRCA2 splice site mutation (IVS16-2A>G) in three breast cancer-only families. This cancer-linked mutation could not be identified in three families with ovarian cancer, suggesting that the mutation predisposes at least predominantly to breast cancer. All mutation carriers shared a common disease associated haplotype indicating a founder effect. This mutation most probably occurred in a single ancestor and seems essentially confined to the Slovene population.

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References

  1. Goelen G, Teugels E, Bonduelle M, Neyns B, De Grève J . High frequency of BRCA 1/2 mutations in 42 Belgian families with a small number of symptomatic subjects J Med Genet 1999 36: 304–308
    CAS PubMed PubMed Central Google Scholar
  2. Ford D, Easton DF, Stratton M et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families Am J Hum Genet 1998 62: 676–689
    Article CAS PubMed Central PubMed Google Scholar
  3. Struewing JP, Abeliovich D, Peretz T et al. The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals Nat Genet 1995 11: 198–200
    Article CAS PubMed Google Scholar
  4. Thorlacius S, Olafsdottir G, Tryggvadottir L et al. A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes Nat Genet 1996 13: 117–119
    Article CAS PubMed Google Scholar
  5. Petrij-Bosch A, Peelen T, Van Vliet M et al. BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients Nat Genet 1997 17: 341–345
    Article CAS PubMed Google Scholar
  6. Pompe-Kirn V, Zakotnik B, Benulic T, Volk N, Skrk J . Prezivetje bolnikov z rakom v Sloveniji. Ljubljana: Onkoloski institut, Register raka za Slovenijo 1997 (Central Slovene Cancer Register, 1997)
  7. Hogervorst FB, Cornelis RS, Bout M et al. Rapid detection of BRCA1 mutations by the protein truncation test Nat Genet 1995 10: 208–212
    Article CAS PubMed Google Scholar
  8. Ganguly T, Dhulipala R, Godmilow L, Ganguly A . High throughput fluorescence-based conformation-sensitive gel electrophoresis (F-CSGE) identifies six unique BRCA2 mutations and an overall low incidence of BRCA2 mutations in high-risk BRCA1-negative breast cancer families Hum Genet 1998 102: 549–556
    Article CAS PubMed Google Scholar
  9. Neuhausen S, Godwin A, Gershoni R et al. Haplotype and phenotype analysis of nine recurrent BRCA-2 mutations in 111 families: results of an international study Am J Hum Genet 1998 62: 1381–1388
    Article CAS PubMed Central PubMed Google Scholar
  10. Gayther SA, Russel P, Harrington P, Antoniou AC, Easton DF, Ponder BA . The contribution of germline BRCA1 and BRCA2 mutations to familial ovarian cancer: no evidence for other ovarian cancer-susceptibility genes Am J Hum Genet 1999 65: 1021–1029
    Article CAS PubMed Central PubMed Google Scholar
  11. Orban TI, Csokay B, Olah E . Sequence alterations can mask each other's presence during screening with SSCP or heteroduplex analysis: BRCA genes as examples Biotechniques 2000 29: 94–98
    Article CAS PubMed Google Scholar
  12. Gayther SA, Mangion J, Russel P et al. Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene Nat Genet 1997 15: 103–105
    Article CAS PubMed Google Scholar
  13. Santarosa M, Dolcetti R, Magri M et al. BRCA1 and BRCA2 genes: role in hereditary breast and ovarian cancer in Italy Int J Cancer 1999 83: 5–9
    Article CAS PubMed Google Scholar

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Acknowledgements

We thank Slovenian physicians and families for their cooperation. Goele Van Hassel and Kurt De Neef are acknowledged for their technical support. This work was supported by a grant from the ‘Wetenschappelijk Fonds Willy Gepts’ of the AZ-VUB.

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Authors and Affiliations

  1. Laboratory of Medical and Molecular Oncology, AZ-VUB (Free University of Brussels), Laarbeeklaan 101, Brussels, 1090, Belgium
    Jacques De Grève & Erik Teugels
  2. Institute of Oncology, Zaloska 2, Ljubljana, 1000, Slovenia
    Mateja Krajc
  3. Familial Cancer Clinic, AZ-VUB, Laarbeeklaan 101, Brussels, 1090, Belgium
    Mateja Krajc, Jacques De Grève, Guido Goelen & Erik Teugels

Authors

  1. Mateja Krajc
  2. Jacques De Grève
  3. Guido Goelen
  4. Erik Teugels

Corresponding author

Correspondence toJacques De Grève.

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Krajc, M., De Grève, J., Goelen, G. et al. BRCA2 founder mutation in Slovenian breast cancer families.Eur J Hum Genet 10, 879–882 (2002). https://doi.org/10.1038/sj.ejhg.5200886

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