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Low incidence of BRCA2 mutations in breast carcinoma and other cancers

Abstract

Inherited mutant alleles of familial tumour suppressor genes predispose individuals to particular types of cancer. In addition to an involvement in inherited susceptibility to cancer, these tumour suppressor genes are targets for somatic mutations in sporadic cancers of the same type found in the familial forms1. An exception is BRCA1, which contributes to a significant fraction of familial breast and ovarian cancer, but undergoes mutation at very low rates in sporadic breast and ovarian cancers2–4. This finding suggests that other genes may be the principal targets for somatic mutation in breast carcinoma. A second, recently identified familial breast cancer gene, BRCA2 (refs 5–8), accounts for a proportion of breast cancer roughly equal to BRCA1. Like BRCA1, BRCA2 behaves as a dominantly inherited tumour suppressor gene. Individuals who inherit one mutant allele are at increased risk for breast cancer, and the tumours they develop lose the wild-type allele by heterozygous deletion9. The BRCA2 coding sequence is huge, composed of 26 exons that span 10,443 bp8. Here we investigate the rate of BRCA2 mutation in sporadic breast cancers and in a set of cell lines that represent twelve other tumour types. Surprisingly, mutations in BRCA2 are infrequent in cancers including breast carcinoma. However, a probable germline mutation in a pancreatic tumour cell line suggests a role for BRCA2 in susceptibility to pancreatic cancer.

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References

  1. Knudson, A.G. All in the (cancer) family. Nature Genet. 5, 103–104 (1993).

    Article  CAS  PubMed  Google Scholar 

  2. Futreal, P.A. et al. BRCA1 mutations in primary breast and ovarian carcinomas. Science 266, 120–122 (1994).

    Article  CAS  PubMed  Google Scholar 

  3. Hosking, L. et al. A somatic BRCA1 mutation in an ovarian tumor. Nature Genet. 9, 343–344 (1995).

    Article  CAS  PubMed  Google Scholar 

  4. Merajver, S.D. et al.Somatic mutations in the BRCA1 gene in sporadic ovarian tumor. Nature Genet. 9, 439–443 (1995).

    Article  CAS  PubMed  Google Scholar 

  5. Wooster, R. et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 265, 2088–2090 (1994).

    Article  CAS  PubMed  Google Scholar 

  6. Thorlacius, S. et al. Linkage to BRCA2 region in hereditary male breast cancer. Lancet 346, 544–545 (1995).

    Article  CAS  PubMed  Google Scholar 

  7. Wooster, R. et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 378, 7 89–792 (1995).

    Article  Google Scholar 

  8. Tavtigian, S.V. et al.The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nature Genet. 12, 1–6 (1996).

    Article  Google Scholar 

  9. Collins, N. et al. Consistent loss of the wild type allele in breast cancers from a family linked to the BRCA2 gene on chromosome 13q12-13. Oncogene 10, 1673–1675 (1995).

    CAS  PubMed  Google Scholar 

  10. Schutte, M. et al. Identification by representational difference analysis of a homozygous deletion in pancreatic carcinoma that lies within the BRCA2 region. Proc. Natl. Acad. Sci. USA 92, 5950–5954 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kamb, A. et al. Response to Rates of p16 (MTS1) Mutations in Primary Tumors with 9p Loss. Cairns et al.1995 Science 265, 416–417 (1994).

    Article  CAS  PubMed  Google Scholar 

  12. Cleton-Jansen, A.M. et al. Loss of heterozygosity in sporadic breast tumours at the BRCA2 locus on chromosome 13q12-q13. Br. J. Cancer 72, 1241–1244 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Neuhausen, S. et al. Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer. Nature Genet. 13, 1 26–128 (1996).

    Article  Google Scholar 

  14. Gonzalez-Zulueta, M. et al. Methylation of the 5′ CpG island of the p16/CDKN2 tumor suppressor gene in normal and a transformed human tissues correlates with gene silencing. Cancer Res. 55 4531–4535 (1995).

    CAS  PubMed  Google Scholar 

  15. Merio, A. et al. 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nature Med. 1, 686–691 (1995).

    Article  Google Scholar 

  16. Yokota, J. et al. Altered expression of the retinoblastoma (RB) gene in small-cell carcinoma of the lung. Oncogene 3, 471–475 (1988).

    CAS  PubMed  Google Scholar 

  17. Hensel, C.H. et al. Altered structure and expression of the human retinoblastoma susceptibility gene in small cell lung cancer. Cancer Res. 50, 3067–3072 (1990).

    CAS  PubMed  Google Scholar 

  18. Vogelstein, B. et al. Allelotype of colorectal carcinomas. Science. 244, 207–211 (1989).

    Article  CAS  PubMed  Google Scholar 

  19. Liu, Q. et al. CDKN2 (MTS1) tumor suppressor gene mutations in human tumor cell lines. Oncogene 10, 1061–1067 (1995).

    CAS  PubMed  Google Scholar 

  20. Emi, M. et al. A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers. Nature Genet. 5, 151–157 (1993).

    Article  CAS  PubMed  Google Scholar 

  21. Richard, I. & Beckmann, J.S. How neutral are synonymous codon mutations? Nature Genet. 10, 259 (1995).

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Alexander K.C. Wong.

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Teng, DR., Bogden, R., Mitchell, J. et al. Low incidence of BRCA2 mutations in breast carcinoma and other cancers. Nat Genet 13, 241–244 (1996). https://doi.org/10.1038/ng0696-241

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