The Tyr978X BRCA1 Mutation in Non-Ashkenazi Jews: Occurrence in High-Risk Families, General Population and Unselected Ovarian Cancer PatientsShiri-Sverdlov R.a · Gershoni-Baruch R.e · Ichezkel-Hirsch G.b · Gotlieb W.H.c · Bruchim Bar-Sade R.a · Chetrit A.b · Rizel S.d · Modan B.b · Friedman E.a
aSusanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Genetics, and Departments of bClinical Epidemiology, cGynecological-Oncology, and dOncology, Chaim Sheba Medical Center, Tel-Hashomer, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, and eGenetics Institute, Rambam Medical Center and the Bruce Rapoport Medical School, Technion, Haifa, Israel
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Background: In Jewish individuals of Ashkenazi (East European) decent, three predominant mutations, 185 delAG and 5382insC (BRCA1) and 6174delT (BRCA2), seem to account for a substantial portion of germline mutations in high-risk breast/ovarian cancer families. Among non-Ashkenazi Jews, the 185delAG and the Tyr978X mutations, as well as several ‘private’ mutations have been reported within the BRCA1 gene. Objective: Assessing the occurrence rate of the Tyr978X BRCA1 germline mutation in Jewish non-Ashkenazi individuals: high-risk familial cases, unselected ovarian cancer patients and the general average risk Jewish Iraqi population. In addition, finding proof that this is a founder mutation. Methods: PCR amplification of the relevant fragment of the BRCA1 gene from constitutional DNA followed by restriction enzyme digest that differentiates the wild type from the mutant allele. In addition, BRCA1-linked markers were used for haplotype analysis. Results: The Tyr978X BRCA1 mutation was detected in 3/289 (1%) of the average-risk Jewish Iraqi population, in 7/408 (1.7%) high-risk Jewish non-Ashkenazi individuals (representing 332 unrelated families) and in 1/81 (1.2%) of unselected Jewish non-Ashkenazi ovarian cancer patients. Allelotyping using BRCA1-linked markers revealed an identical allelic pattern in all mutation carriers with the intragenic markers. Conclusions: Our findings suggest that this mutation is prevalent in Iraqi Jews, represents a founder mutation, and should be incorporated into the panel of mutations analyzed in high-risk families of the appropriate ethnic background.
© 2001 S. Karger AG, Basel
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