title: Somatic and germline mutations of the BRCA2 gene in sporadic ovarian cancer.
abstract: The breast and ovarian cancer susceptibility gene BRCA2 has recently been isolated. A role for BRCA2 in sporadic breast and ovarian cancer has been suggested by loss of heterozygosity (LOH) studies which show frequent LOH in the BRCA2 region at chromosome 13q12. In addition, the observation of nonrandom loss of the wild-type chromosome in a breast/ovarian cancer family which shows linkage to BRCA2 suggests it may act as a tumor suppressor gene. To determine the extent of somatic alteration involving BRCA2 in sporadic ovarian cancer, 50 tumors were analyzed for mutations throughout the entire BRCA2 coding region. Mutations predicted to result in truncation of the BRCA2 protein were detected in four tumors. Analysis of germline DNA revealed two of these alterations to be of somatic origin. In addition, all four tumors exhibited loss of the second BRCA2 allele as predicted by Knudson's hypothesis for a tumor suppressor gene. These results suggest that, as is the case with BRCA1, somatic mutations of BRCA2 are infrequent in sporadic ovarian cancer, despite the relatively high frequency of LOH detected around the BRCA2 locus.
authors.affiliation: Cancer Research Campaign Human Cancer Genetics Research Group, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: K A
authors.initials: KA
authors.lastname: Foster
authors.forename: P
authors.initials: P
authors.lastname: Harrington
authors.forename: J
authors.initials: J
authors.lastname: Kerr
authors.forename: P
authors.initials: P
authors.lastname: Russell
authors.forename: R A
authors.initials: RA
authors.lastname: DiCioccio
authors.forename: I V
authors.initials: IV
authors.lastname: Scott
authors.forename: I
authors.initials: I
authors.lastname: Jacobs
authors.forename: G
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
authors.forename: S A
authors.initials: SA
authors.lastname: Gayther
mesh_terms: D024682:BRCA2 Protein; D002872:Chromosome Deletion; D005260:Female; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors