Assessments of breast cancer (BC) risk in carriers of pathogenic variants identified by gene panel testing in different populations are highly in demand worldwide. We performed target sequencing of 78 genes involved in DNA repair in 860 females with BC and 520 age- and family history-matched controls from Central Russia. Among BC patients, 562/860 (65.3%) were aged 50 years or less at the time of diagnosis. In total, 190/860 (22%) BC patients were carriers of 198 pathogenic/likely pathogenic (P/LP) variants in 30 genes, while among controls, 32/520 (6.2%) carriers of P/LP variants in 17 genes were identified. The odds ratio [95% confidence interval] was 16.3 [4.0–66.7] for BRCA1; 12.0 [2.9–45.9] for BRCA2; and 7.3 [0.9–56.7] for ATM (p < 0.05). Previously undescribed BRCA1/2, ATM, and PALB2 variants, as well as novel recurrent mutations, were identified. The contribution to BC susceptibility of truncating variants in the genes BARD1, RAD50, RAD51C, NBEAL1 (p. E1155*), and XRCC2 (p. P32fs) was evaluated. The BLM, NBN, and MUTYH genes did not demonstrate associations with BC risk. Finding deleterious mutations in BC patients is important for diagnosis and management; in controls, it opens up the possibility of prevention and early diagnostics.

Aim of the study– to analyze the molecular genetic profile of rare melanocytic tumors in children, including skin melanoma.Materials and methods.The study of melanocytic neoplasms tissue samples of 11 pediatric patients with melanocytic tumors was carried out by the method of targeted genomic DNA sequencing. The coding regions of genes involved in the processes of melanogenesis, melanomogenesis, proliferation, cell adhesion were investigated.Results.It was found that in two cases in giant congenital melanocytic nevi there were mutations in the NRASgene, the same mutations were found in samples of melanomas that developed against the background of these nevi. In both cases, the developed melanomas were highly malignant. In one patient, a mutation in the CTNNB1 gene was detected in a melanoma sample, which is absent in the nevi tissue cells. In two cases of Spitz nevus, in the lentignous melanocytic nevus and in the Reed nevus, mutations in the promoter region of the TERTgene (c.-269G A and c.-348G C) were detected. The V600E mutation in the BRAFgene was found in dysplastic nevus and Reed nevus; in the latter case, its combination with mutations in the TERT gene promoter was revealed.In a sample of a blue nevus, the p.Q209L mutation in the GNAQ gene was detected, which is a pathognomonic genetic aberration, associated with this type of melanocytic nevus.Conclusion.The study of the spectrum of mutations in samples of children with rare melanocytic tumors, including melanoma, indicates that the type of mutation identified was largely associated with the clinical characteristics of the nevus.