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Background. Breast cancer (BC) is the most common female malignancy worldwide. partner and localizer of BRCA2 gene (PALB2) is directly involved in DNA damage response. germline mutation in PALB2 has been identified in breast cancer and familial pancreatic cancer cases, accounting for approximately 1–2% and 3–4%, respectively. the goal of this report was to describe new PALB2 mutation in a young Yakut breast cancer patient with family history of cancer. Material and methods. Genomic DNA were isolated from blood samples and used to prepare libraries using a capture-based target enrichment kit, Hereditary Cancer Solution™ (SOPHIA GENETICS, Switzerland), 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). paired-end sequencing (2 × 150 bp) was conducted using NextSeq 500 system (Illumina, USA). Results. Here we describe a case of a never-before-reported mutation in the PALB gene that led to the early onset breast cancer. We report the case of a 39-year-old breast cancer Yakut woman with a family history of pancreatic cancer. Bioinformatics analysis of the NGS data revealed the presence of the new PALB2 gene germinal frameshift deletion (NM_024675:exon1:c.47dela:p.K16fs). in accordance with dbPubMed ClinVar, new mutation is located in codon of the PALB2 gene, where the likely pathogenic donor splice site mutation (NM_024675.3:c.48+1delG) associated with hereditary cancer-predisposing syndrome has been earlier described. Conclusion. We found a new never-before-reported mutation in PALB2 gene, which probably associated with early onset breast cancer in Yakut indigenous women with a family history of pancreatic cancer.

Background. The identification of the ethnospecific mutations associated with hereditary breast cancer remains challenging. Next generation sequencing (Ngs) technology fully enables the compilation of germline variants associated with the risk for inherited diseases. Despite the success of the Ngs, up to 20 % of molecular tests report genetic variant of unknown significance (Vus) or novel variants that have never been previously described and their clinical significances are unknown. To obtain extended information about the variants of the unknown significance, it is necessary to use an alternative approach for the analysis of the Ngs data. To obtain extended characteristic about the unknown significance variants, it is necessary to search for additional tools for the analysis of the Ngs data. Material and methods. We reclassified the mutation of the unknown significance using the activedrivedb database that assessed the effect of mutations on sites of post-translational modifications, and the proteinpaint tool that complemented the existing cancer genome portals and provided a comprehensive and intuitive view of cancer genomic data. Results. In this study, we report a 44-year-old tuvinian woman with a family history of breast cancer. Based on the Ngs data, mutational analysis revealed the presence of the lrg_321t1: c.80c>t heterozygous variant in exon 2, which led to the proline to leucine change at codon 27 of the protein. In the dbpubmed database, this mutation was determined as unknown significance due to data limitation. According to the data of the activedriverdb tool, this mutation is located distally at the site of post-translational protein modification, which is responsible for binding to kinases that regulate genes of the cell cycle, etc. (atm, chek2, cdk, mapk). In accordance with proteinpaint tool, the lrg_321t1: c.80c>t mutation is located in functionally specialized transactivation domains and codon of the tp53 gene, where the pathogenic mutation associated with li-Fraumeni syndrome has been earlier described. Conclusion. This report is the first to describe a new variant in the tp53 gene (rs1555526933), which is likely to be associated with hereditary cancer-predisposing syndrome, including li-Fraumeni syndrome, in a tuvinian Bc patient with young-onset and familial Bc.

This studyaimed to reveal the spectrum of BRca1 and BRca2 genes mutation in various ethnic groups of the Russian Federation. asystematic literature search includes data for the past 10 years and was conducted by using electronic databases of pubmed, eliBRaRY and ect.Material and methods.The review includes research data on the frequency of mutations of breast cancer-associated genes in various ethnic groups of the Russian Federation.Results.For «slavic» patients with a family history, the BRca1/2 mutation testing is the standard of care. in addition, the development of new antitumour drugs has resulted in improved survival rates. more than 1000 mutations of the BRca1 gene have been identified. Recent research is focused on the confirmation the beneficial effect of identified mutations. For the indigenous population (mongoloid ethnic groups), there are no standards for the treatment of inherited breast cancer. thus, the advances in molecular oncology for the treatment of hereditary breast cancer are not available for the indigenous population of the Russian Federation.Conclusion.In this context, the search for markers of early cancer detection and the development of criteria for therapy response are relevant for indigenous people. the development of new predictive and prognostic criteria of breast cancer among mongoloid ethnic groups with a family history will allow the innovative strategies for personalized molecular therapy to be developed.