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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Knudson, A.G. All in the (cancer) family. Nature Genet. 5, 103–104 (1993).
Futreal, P.A. et al. BRCA1 mutations in primary breast and ovarian carcinomas. Science 266, 120–122 (1994).
Hosking, L. et al. A somatic BRCA1 mutation in an ovarian tumor. Nature Genet. 9, 343–344 (1995).
Merajver, S.D. et al.Somatic mutations in the BRCA1 gene in sporadic ovarian tumor. Nature Genet. 9, 439–443 (1995).
Wooster, R. et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 265, 2088–2090 (1994).
Thorlacius, S. et al. Linkage to BRCA2 region in hereditary male breast cancer. Lancet 346, 544–545 (1995).
Wooster, R. et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 378, 7 89–792 (1995).
Tavtigian, S.V. et al.The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nature Genet. 12, 1–6 (1996).
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).
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).
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).
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).
Neuhausen, S. et al. Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer. Nature Genet. 13, 1 26–128 (1996).
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).
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).
Yokota, J. et al. Altered expression of the retinoblastoma (RB) gene in small-cell carcinoma of the lung. Oncogene 3, 471–475 (1988).
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).
Vogelstein, B. et al. Allelotype of colorectal carcinomas. Science. 244, 207–211 (1989).
Liu, Q. et al. CDKN2 (MTS1) tumor suppressor gene mutations in human tumor cell lines. Oncogene 10, 1061–1067 (1995).
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).
Richard, I. & Beckmann, J.S. How neutral are synonymous codon mutations? Nature Genet. 10, 259 (1995).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0696-241
This article is cited by
-
A reliable method for the detection of BRCA1 and BRCA2 mutations in fixed tumour tissue utilising multiplex PCR-based targeted next generation sequencing
BMC Clinical Pathology (2015)
-
Reevaluation of the BRCA2 truncating allele c.9976A > T (p.Lys3326Ter) in a familial breast cancer context
Scientific Reports (2015)
-
Treatment options for patients with triple-negative breast cancer
Journal of Hematology & Oncology (2010)
-
Mammary cancer susceptibility: human genes and rodent models
Mammalian Genome (2007)
-
Low frequency of somatic mutations in the FH/multiple cutaneous leiomyomatosis gene in sporadic leiomyosarcomas and uterine leiomyomas
British Journal of Cancer (2002)