Mutational analysis of BRCA1 gene in ovarian and breast-ovarian cancer families in Japan.
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.
Takano
M
M
Department of Obstetrics and Gynecology, Niigata University School of Medicine, Asahimachi-Dori.
Aida
H
H
Tsuneki
I
I
Takakuwa
K
K
Hasegawa
I
I
Tanaka
H
H
Saito
M
M
Tsuji
S
S
Sonoda
T
T
Hatae
M
M
Chen
J T
JT
Takahashi
K
K
Hasegawa
K
K
Toyoda
N
N
Saito
N
N
Yakushiji
M
M
Araki
T
T
Tanaka
K
K
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
D019313:BRCA1 Protein