title: Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.
abstract: We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.
authors.affiliation: Department of Obstetrics and Gynecology, Niigata University School of Medicine, 1-757, Asahimachi-dori, Niigata City 951-8510, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sekine
authors.forename: H
authors.initials: H
authors.lastname: Nagata
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
authors.forename: Y
authors.initials: Y
authors.lastname: Hirai
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
authors.forename: M
authors.initials: M
authors.lastname: Hatae
authors.forename: I
authors.initials: I
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Fujii
authors.forename: I
authors.initials: I
authors.lastname: Nagata
authors.forename: K
authors.initials: K
authors.lastname: Ushijima
authors.forename: K
authors.initials: K
authors.lastname: Obata
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Yoshinaga
authors.forename: N
authors.initials: N
authors.lastname: Umesaki
authors.forename: S
authors.initials: S
authors.lastname: Satoh
authors.forename: T
authors.initials: T
authors.lastname: Enomoto
authors.forename: S
authors.initials: S
authors.lastname: Motoyama
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D018703:Founder Effect; D016368:Frameshift Mutation; D005787:Gene Frequency; D005843:Geography; D006801:Humans; D007564:Japan; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D018389:Codon, Nonsense; D004273:DNA, Neoplasm