High frequency of recurrent mutations in BRCA1 and BRCA2 genes in Polish families with breast and ovarian cancer

Germ-line mutations in BRCA1 and BRCA2 genes result in a significantly incr eased risk of breast and ovarian cancer, Other genes involved in an increas ed predisposition to breast cancer include the TP53 gene, mutated in Li-Fra umeni syndrome. To estimate the frequency of germline mutations in these th ree genes in Upper Silesia, we have analyzed 47 breast/ovarian cancer famil ies from that region. We found five different disease predisposing mutation s in 17 (36%) families. Twelve families (25.5%) carried known BRCA1 mutatio ns (5382insC and C61G), four families (8.5%) carried novel BRCA2 mutations (9631delC and 6886delGAAAA), and one family (2%) harbored novel mutation 10 95del8 in the TP53 gene, which is the largest germline deletion in coding s equence of this gene identified thus far, The 5382insC mutation in BRCA1 wa s found in 11 families and the 9631delC mutation in BRCA2 occurred in three families. These two mutations taken together contribute to 82% of all muta tions found in this study, and 30% of the families investigated harbor one of these mutations. The very high frequency of common mutations observed in these families can only be compared to that reported for Ashkenazi Jewish, Icelandic, and Russian high-risk families. This frequency, however, may no t be representative for the entire Polish population. The observed distribu tion of mutations will favor routine pre-screening of predisposed families using a simple and cost-effective test. Hum Mutat 16:482-490, 2000. (C) 200 0 Wiley-Liss, Inc.