title: 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 forms. 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 cancers. 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 deletion. The BRCA2 coding sequence is huge, composed of 26 exons that span 10,443 bp. 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.
authors.affiliation: Myriad Genetics, Inc., Salt Lake City, Utah 84108, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Teng
authors.forename: R
authors.initials: R
authors.lastname: Bogden
authors.forename: J
authors.initials: J
authors.lastname: Mitchell
authors.forename: M
authors.initials: M
authors.lastname: Baumgard
authors.forename: R
authors.initials: R
authors.lastname: Bell
authors.forename: S
authors.initials: S
authors.lastname: Berry
authors.forename: T
authors.initials: T
authors.lastname: Davis
authors.forename: P C
authors.initials: PC
authors.lastname: Ha
authors.forename: R
authors.initials: R
authors.lastname: Kehrer
authors.forename: S
authors.initials: S
authors.lastname: Jammulapati
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Offit
authors.forename: M H
authors.initials: MH
authors.lastname: Skolnick
authors.forename: S V
authors.initials: SV
authors.lastname: Tavtigian
authors.forename: S
authors.initials: S
authors.lastname: Jhanwar
authors.forename: B
authors.initials: B
authors.lastname: Swedlund
authors.forename: A K
authors.initials: AK
authors.lastname: Wong
authors.forename: A
authors.initials: A
authors.lastname: Kamb
mesh_terms: D024682:BRCA2 Protein; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D002277:Carcinoma / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors