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Background. The Sakha (Yakutia) population, the indigenous population of Siberia living in Yakutia, has one of the lowest rates of breast cancer (BC) incidence worldwide. The low BC incidence among the indigenous population of Yakutia has been reported by several authors, but to date the reasons for this phenomenon have not been fully elucidated. It should be noted that the study of factors that reduce the risk of BC is important for its prevention. In several studies, no hereditary BC was found in the Yakuts, and no pathogenic variants of the BRCA1/2 genes associated with hereditary syndromes of breast and ovarian cancers were found. In this regard, we decided to shift the focus to studying the mitochondrial genome of Sakha BC patients using the sequencing method.The purpose of the study was to identify BC-associated mitochondrial genome variants in Sakha patients.Material and Methods. The study included 14 Sakha patients diagnosed with BC. The median age of the patients was 49 years. DNA isolation was performed using phenol-chloroform extraction. DNA libraries were prepared using the Nextera Flex kit (Illumina, USA).Whole-genome sequencing of the mitochondrial genome was performed on a MiSeq instrument (Illuminа, USA). in the Shared Use Centre of the Research Institute of Medical Genetics, Tomsk National Research Centre of the Russian Academy of Sciences. The results obtained in BC patients were compared with those of control subjects.Results. In Sakha women with BC, 159 mitochondrial genome variants that differed from the human mitochondrial DNA (mtDNA) reference sequence (rCRS) were identified. Likely pathogenic variants m.3736G>A of the MT-ND1 gene and m.7279T>C of the MT-CO1 gene were shown to be associated with BC. For the first time, variants predisposing to BC (m.10398A>G; m.14783T>C; m.15043G>A; m.15301G>A) were identified. A distinctive feature of the mitochondrial genome of populations with a low BC incidence is a high level of mtDNA variants with changes in the length of the polycytosine region in the D310 locus.Conclusion. For the first time, mtDNA variants with changes in the length of the polycytosine tract in the D310 locus and likely pathogenic variants m.3736G>A of the MT-ND1 gene and m.7279T>C of the MT-CO1 gene were identified in Sakha BC women. The data obtained indicate that further studies on the role of the identified mtDNA variants in the development of BC using a larger sample of Sakha patients are required.

The purpose of the study: to analyze the breast cancer incidence and breast cancer risk factors for the population of the Republic of Sakha (Yakutia) in 2011-2020. Material and Methods. The incidence of breast cancer in the population of Yakutia was analyzed using the data collected from population-based cancer registries of the Russian cancer statistics covering the period 2011-2020. The analysis of breast cancer risk factors was carried out using the data from systematic reviews published over the past 5 years (2018-2022). Results. The age-standardized incidence rates of breast cancer among the indigenous population of the Republic of Sakha (Yakutia) were lower than those in other Siberian ethnic groups and the Slavic population, amounting to 12.7 per 100,000 population. The rise in the breast cancer incidence rates in the region for 2011-2020 was associated with the aging of the population, since the trend in the population growth was not observed in the analysis of age-standardized rates. Conclusion. The breast cancer incidence rates among the indigenous population of the Republic of Sakha (Yakutia) are significantly lower compared to those observed in other ethnic groups living in Siberia. The rise in the breast cancer incidence rates in Yakutia is related to the aging of the population. The low age-standardized breast cancer incidence rates may be explained by a low consumption of hormonal agents and natural reproductive behavior. The search for ethno-specific mutations associated with breast cancer in the Yakut population as endogenous risk factors is of great importance. Further studies are required to elucidate the role of North-adaptive genetic mutations in the development of breast cancer. The assessment of the role of natural polyphenolic compounds, the content of which is high in wild berries (historically, a significant proportion of the food consumed by indigenous people), as a protective factor, is promising.

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™ (SOP HiA GE NETICS , 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 PALB2 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 study aimed 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.

Relevance. Classification of organomineral soils according to state standards require correction. Methods for determining classification consistency indicators give excessive values moisture content of the plasticity and liquid limits due to the high content of organic matter. Due to imperfect standards, their results are unreliable and the grounds are incorrectly classified, which leads to errors in calculations of the base of constructions. The expediency of determining the consistency of organics containing soils is doubtful, and in order to reduce costs in engineering and geological investigations, the authors propose to consider in detail the problem of classification of organomineral soils by the example of numerous experimental data obtained for soils in the West Siberian region and recommend еру changes to existing standards. The main aim of the research is to identify the relationship between consistency indicators and organic matter content based on the experimental studies of organic-mineral soils of Western Siberia and justify the use of the Atterberg limits applied for mineral soils. Object: organomineral clay soils typical for Western Siberia, picked on the territory surroundings of the city of Tomsk, oil and gas fields of Tomsk region and Khanty-Mansiysky Autonomous District. Research methods include a method for determining limits of liquid and plasticity (wL and wp) and organic content (Ir), as well as by analyzing the results using MS Excel and Statistica. Results. The authors have carried out the review and analysis of foreign methods for determining the classification indexes of consistency in engineering-geological surveys and considered the problems of their carrying out and applications for soils containing organic substances. The determinations of organic matter, moisture content and consistency were carried out, significant interrelations between the indices were obtained and regression equations were compiled. As a result, inconsistencies with the current classification of organomineral clay soils due to overestimation of the consistency indices are revealed, therefore, in relation to their uninformativeness, it is recommended to abandon their use for organics containing soils.