New germline mutations in BRCA1, ATM, MUTYH, and RAD51D genes in Tuvans early-onset breast cancer patients.

Abstract

BACKGROUND\nIn Russia, more than 50,000\xa0women are diagnosed with breast cancer (BC) every year. Russia is a multinational country\xa0- about 200\xa0ethnic groups live on its territory. Khakass, Buryats, Tuvans and other ethnic groups show higher rate of increase in BC incidence and a younger age of first diagnosed BC compared to Caucasian ethnicities. We focused on Tuvan ethnic group to find specific genetic aberrations associated with BC. There are no BC prevention models as well as standards for the treatment of inherited BC in Tuvans. In this context, the search for genetic markers of early cancer detection and the development of criteria for therapy response are relevant.\n\n\nAIM\nTo identify hereditary mutations in BC-associated genes in Tuvan women.\n\n\nMATERIALS AND METHODS\n24\xa0patients with early-onset BC (range, 25\xa0to 46\xa0years) were enrolled in the study. Genomic DNA isolated from blood samples was used to prepare libraries using a capture-based target enrichment kit covering 27\xa0genes (ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, PMS2CL, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53\xa0and XRCC2). Next-generation sequencing was performed using the Illumina NextSeq500\xa0System.\n\n\nRESULTS\nIn our study, one pathogenic mutation was detected in BRCA1 (rs80357868) gene (prevalence of 4%, 1/24). We identified the truncating 3875_3878delGTCT mutation of BRCA1\xa0gene in Tuvans BC patient aged 34\xa0years. We also detected three mutations that were probably damaging by PolyPhen2\xa0and/or deleterious by SIFT in ATM (rs781023264), MUTYH (rs199840380) and RAD51D (rs145309168) genes.\n\n\nCONCLUSION\nTo the best of our knowledge, this is the first report that describes the highly pathogenic variant in the BRCA1\xa0gene (rs80357868) and possibly damaging (PolyPhen2) germline variants in the ATM (rs781023264), MUTYH (rs199840380) and RAD51D (rs145309168) genes in young Tuvans BC patient.