Ashkenazi founder BRCA1/BRCA2 mutations in Slovak hereditary breast and/or ovarian cancer families.

Germline mutations in BRCA1 and BRCA2 have been predominantly associated with the breast and ovarian cancers. Two mutations in BRCA1 (185delAG and 5382insC) and one mutation in BRCA2 (6174delT) are common in Ashkenazi Jewish population. To determine the proportion of these founder mutations, we analyzed DNA samples of 120 Slovak hereditary breast and/or ovarian cancer (HBOC) suspected families. Two particular exons of BRCA1 (2, 20) and 11N segment of BRCA2 were screened by single strand conformation polymorphism (SSCP) followed by DNA sequencing of fragments showing abnormal migration pattern. Mutational analysis revealed that 7 out of 20 (35%) families with detected BRCA1/BRCA2 pathogenic alteration harbored one of three Jewish mutations: five families with 5382insC, one family with 185delAG and one family with 6174delT. Interestingly, we have noted a very rare phenotype, when 5382insC in BRCA1 co-segregated also with endometrial carcinoma. Similarly to the studies from other countries of Central and Eastern Europe, the most frequent pathogenic alteration found was 5382insC that accounted for 1/4 of all gene defects detected. Following the high proportion of Ashkenazi Jewish founder mutations in Slovak HBOC families, a pre-screening for at least 5382insC mutation in individuals at even moderate risk would be appropriate.