Mutations in BRCA1 and BRCA2 in breast cancer families: Are there more breast cancer-susceptibility genes?

Olga M. Serova, Sylvie Mazoyer, Nadine Puget, Valérie Dubois, Patricia Tonin, Yin Y. Shugart, David Goldgar, Steven A. Narod, Henry T. Lynch, Gilbert M. Lenoir

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

To estimate the proportion of breast cancer families due to BRCA1 or BRCA2, we performed mutation screening of the entire coding regions of both genes supplemented with linkage analysis of 31 families, 8 containing male breast cancers and 23 site-specific female breast cancer. A combination of protein-truncation test and SSCP or heteroduplex analyses was used for mutation screening complemented, where possible, by the analysis of expression level of BRCA1 and BRCA2 alleles. Six of the eight families with male breast cancer revealed frameshift mutations, two in BRCA1 and four in BRCA2. Although most families with female site-specific breast cancers were thought to be due to mutations in either BRCA1 or BRCA2, we identified only eight mutations in our series of 23 site-specific female breast cancer families (34%), four in BRCA1 and four in BRCA2. According to the posterior probabilities calculated for mutation-negative families, based on linkage data and mutation screening results, we would expect 8-10 site-specific female breast cancer families of our series to be due to neither BRCA1 nor BRCA2. Thus, our results suggest the existence of at least one more major breast cancer-susceptibility gene.

Original languageEnglish (US)
Pages (from-to)486-495
Number of pages10
JournalAmerican journal of human genetics
Volume60
Issue number3
StatePublished - Mar 1 1997

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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    Serova, O. M., Mazoyer, S., Puget, N., Dubois, V., Tonin, P., Shugart, Y. Y., Goldgar, D., Narod, S. A., Lynch, H. T., & Lenoir, G. M. (1997). Mutations in BRCA1 and BRCA2 in breast cancer families: Are there more breast cancer-susceptibility genes? American journal of human genetics, 60(3), 486-495.