Introduction. The hereditary predisposition to the growth of breast cancer (BC), associated with germline mutations of DNA genes repair (BRCA(1,2)), is characterized by a variety of polymorphism variants, with a tendency to a certain specificity in different population groups. In regions with a mixed population composition, such as Crimean Peninsula, the problem of the relationship of specific mutations and a population group is not only of scientific interest, but also has rather important practical significance from the point of view of diagnostic and prognostic criteria design for the breast cancer incidence.
The aim of the study was to determine the frequency of occurrence of BRCA1 (5382insC, 4153delA, 185delAG) and BRCA2 (6174delT) genes mutations in two population groups having a breast cancer and living in the Crimea - Slavic and Crimean Tatar, with clinical signs of a hereditary disease.
Materials and methods. 283 DNA samples were studied, collected from the blood of patients with clinical signs of hereditary breast cancer, of which 208 were Slavic and 75 were Crimean Tatar population group. The control group consisted of 256 DNA samples collected from the blood of healthy women, of which 196 were Slavic and 60 were Crimean Tatar population group. The study was carried out using real-time polymerase chain reaction (PCR-RT) by allelic discrimination, with the analysis of melting curves. Morphological verification of the diagnosis was carried out by a set of methods for determining the histological variant and tumor immunophenotyping according to the standard diagnostic program.
Results. Mutations were detected in 23 breast cancer cases; these mutations were determined exclusively in the Slavic group. The 5382insC BRCA1 gene mutation was prevailed (21/10,1%), and 185delAG BRCA1 mutations one case and 6174delT BRCA2 mutation one case were obtained. None of the gene mutation was not registered in the Crimean Tatar population group. Immunohistochemi-cally triple negative breast cancer was determined in 86.4% of mutations cases. Only one case of mutation was recorded in the control group - 5382insC of the BRCA1 gene in the Slavic population group (0,4%).
Conclusion. The frequency of occurrence of the “founder mutation” 5382insC BRCA1 gene mutation in breast cancer patients from Slavic population group corresponds to the average Russian and European levels, the frequency of other variants of the studied mutations, 185delAG BRCA1 gene and 6174delT BRCA2 gene, is recorded much less frequently, and the 4153delA mutation was not observed in the studied samples. The absence of mutations in the studied markers of the Crimean Tatars population group, including those with a hereditary predisposition to breast cancer, indicates differences in the mutation spectrum and necessitates the continuation of studies with an expansion of the mutation spectrum, with the prospect of full-genome (BRCA1) or genome-wide DNA sequencing of patients.
WT1 gene mutation in exone 7 in boy with disturbance of the sex formation and the bilateral nephroblastoma
