New germline mutations in BRCA1, ATM, MUTYH, and RAD51D genes in Tuvans early-onset breast cancer patients
| Autor: | A Chernyshova, Artem Kiselev, Ye Panferova, Polina Gervas, A. Ivanova, A. Molokov, Lubov Pisareva, N. Cherdyntseva, Evgeny Choynzonov |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Adult Cancer Research medicine.medical_specialty PALB2 RAD51D ген Genes BRCA1 Context (language use) Breast Neoplasms Ataxia Telangiectasia Mutated Proteins MLH1 DNA Glycosylases Russia Germline mutation MUTYH Internal medicine medicine Biomarkers Tumor Ethnicity Humans Genetic Predisposition to Disease тувинцы Age of Onset CHEK2 рак молочной железы Germ-Line Mutation мутации зародышевой линии business.industry BRCA1 Protein Incidence Middle Aged BRCA1 ген ATM ген MSH6 DNA-Binding Proteins MSH2 MUTYH ген Female business |
| Zdroj: | Experimental oncology. 2021. Vol. 43, № 1. P. 52-55 |
| Popis: | Background In Russia, more than 50,000 women are diagnosed with breast cancer (BC) every year. Russia is a multinational country - about 200 ethnic 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. Aim To identify hereditary mutations in BC-associated genes in Tuvan women. Materials and methods 24 patients with early-onset BC (range, 25 to 46 years) 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 genes (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 and XRCC2). Next-generation sequencing was performed using the Illumina NextSeq500 System. Results In 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 gene in Tuvans BC patient aged 34 years. We also detected three mutations that were probably damaging by PolyPhen2 and/or deleterious by SIFT in ATM (rs781023264), MUTYH (rs199840380) and RAD51D (rs145309168) genes. Conclusion To the best of our knowledge, this is the first report that describes the highly pathogenic variant in the BRCA1 gene (rs80357868) and possibly damaging (PolyPhen2) germline variants in the ATM (rs781023264), MUTYH (rs199840380) and RAD51D (rs145309168) genes in young Tuvans BC patient. |
| Databáze: | OpenAIRE |
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