Mutational analysis of BRCA1 gene in ovarian and breast-ovarian cancer families in Japan

Jpn J Cancer Res. 1997 Apr;88(4):407-13. doi: 10.1111/j.1349-7006.1997.tb00397.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • BRCA1 Protein / genetics*
  • Breast Neoplasms / genetics*
  • DNA Mutational Analysis
  • Female
  • Gene Deletion
  • Heterozygote
  • Humans
  • Japan
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Pedigree
  • Point Mutation


  • BRCA1 Protein