title: BRCA2 mutations in primary breast and ovarian cancers.
abstract: The second hereditary breast cancer gene, BRCA2, was recently isolated. Germline mutations of this gene predispose carriers to breast cancer, and, to a lesser extent, ovarian cancer. Loss of heterozygosity (LOH) at the BRCA2 locus has been observed in 30-40% of sporadic breast and ovarian tumours, implying that BRCA2 may act as a tumour suppressor gene in a proportion of sporadic cases. To define the role of BRCA2 in sporadic breast and ovarian cancer, we screened the entire gene for mutations using a combination of techniques in 70 primary breast carcinomas and in 55 primary epithelial ovarian carcinomas. Our analysis revealed alterations in 2/70 breast tumours and none of the ovarian carcinomas. One alteration found in the breast cancers was a 2-basepair (bp) deletion (4710delAG) which was subsequently shown to be a germline mutation, the other was a somatic missense mutation (Asp3095Glu) of unknown significance. Our results suggest that BRCA2 is a very infrequent target for somatic inactivation in breast and ovarian carcinomas, similar to the results obtained for BRCA1.
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Lancaster
authors.forename: R
authors.initials: R
authors.lastname: Wooster
authors.forename: J
authors.initials: J
authors.lastname: Mangion
authors.forename: C M
authors.initials: CM
authors.lastname: Phelan
authors.forename: C
authors.initials: C
authors.lastname: Cochran
authors.forename: C
authors.initials: C
authors.lastname: Gumbs
authors.forename: S
authors.initials: S
authors.lastname: Seal
authors.forename: R
authors.initials: R
authors.lastname: Barfoot
authors.forename: N
authors.initials: N
authors.lastname: Collins
authors.forename: G
authors.initials: G
authors.lastname: Bignell
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: R
authors.initials: R
authors.lastname: Hamoudi
authors.forename: C
authors.initials: C
authors.lastname: Larsson
authors.forename: R W
authors.initials: RW
authors.lastname: Wiseman
authors.forename: A
authors.initials: A
authors.lastname: Berchuck
authors.forename: J D
authors.initials: JD
authors.lastname: Iglehart
authors.forename: J R
authors.initials: JR
authors.lastname: Marks
authors.forename: A
authors.initials: A
authors.lastname: Ashworth
authors.forename: M R
authors.initials: MR
authors.lastname: Stratton
authors.forename: P A
authors.initials: PA
authors.lastname: Futreal
mesh_terms: D000368:Aged; D024682:BRCA2 Protein; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D017931:DNA Primers; D005819:Genetic Markers; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors