title: Mutational analysis of BRCA1 gene in ovarian and breast-ovarian cancer families in Japan.
abstract: We analyzed the alteration of BRCA1 in DNA obtained from 83 individuals of 13 Japanese site-specific ovarian cancer families and 6 breast-ovarian cancer families. Six germline mutations were detected in 7 families, which consisted of 4 breast-ovarian cancer and 3 site-specific ovarian cancer families, by single-strand conformation polymorphism analysis, followed by direct sequence determination. The mutations included three frameshifts, two nonsense mutations, and one missense mutation causing loss of a zinc-binding motif. The frequency of loss of heterozygosity at the microsatellite markers on the BRCA1 gene was 57% (8 of 14 cases) in site-specific ovarian cancer families, and 100% (6 of 6 cases) in breast-ovarian cancer families. All tumors of the patients carrying a mutation of BRCA1 showed deletion of wild-type alleles, implicating BRCA1 as a tumor suppressor gene. These results suggest that germline mutations of the BRCA1 gene play an important role in the carcinogenesis of breast and/or ovarian cancer in a majority of breast-ovarian cancer families and in some site-specific ovarian cancer families.
authors.affiliation: Department of Obstetrics and Gynecology, Niigata University School of Medicine, Asahimachi-Dori.
authors.forename: M
authors.initials: M
authors.lastname: Takano
authors.forename: H
authors.initials: H
authors.lastname: Aida
authors.forename: I
authors.initials: I
authors.lastname: Tsuneki
authors.forename: K
authors.initials: K
authors.lastname: Takakuwa
authors.forename: I
authors.initials: I
authors.lastname: Hasegawa
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
authors.forename: T
authors.initials: T
authors.lastname: Sonoda
authors.forename: M
authors.initials: M
authors.lastname: Hatae
authors.forename: J T
authors.initials: JT
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Hasegawa
authors.forename: N
authors.initials: N
authors.lastname: Toyoda
authors.forename: N
authors.initials: N
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Yakushiji
authors.forename: T
authors.initials: T
authors.lastname: Araki
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation
chemical_list: D019313:BRCA1 Protein