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.

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.

Введение. Проблема идентификации в российских популяциях этноспецифических мутаций, ассоциированных с наследственными формами рака молочной железы, остается открытой. Технология высокопроизводительного секвенирования является методом выбора, однако существуют сложности интерпретации полученного массива данных при аннотировании их с использованием общепринятых баз данных. Так, для малоизученных популяций от 20 % молекулярных тестов сообщают о генетических вариантах неизвестного значения (Vus) или новых вариантах, которые ранее не были описаны. Для получения расширенной информации о вариантах высокопроизводительного секвенирования неизвестного значения необходимо использовать альтернативные подходы анализа данных. Материал и методы. Проведена реклассификация мутации неизвестного значения гена ТР53 с использованием базы данных activedrivedB, которая оценивает влияние мутаций на сайты посттрансляционных модификаций, и инструмента proteinpaint, который обеспечивает всестороннее и интуитивно понятное представление о геномных данных. Результаты. Мутация гена tp53 (rs1555526933) была обнаружена у молодой тувинки 44 лет с диагнозом РМЖ. В базе данных dbpubmed (rs1555526933, chr17:7579716, g>a, pro27leu) эта мутация является вариантом неизвестного значения (unknown significance) с отсутствием информации о частоте встречаемости минорного аллеля. Согласно данным инструмента activedriverdB, эта мутация расположена дистально в сайте посттрансляционной модификации белков, отвечающем за связывание с киназами, регулирующими гены клеточного цикла и др. (atm, cHeK2, cdK, mapK). Согласно данным proteinpoint, эта мутация находится в кодоне, где ранее была описана патогенная мутация гена tp53 p.leu26glnfster4 (Nm_000546.6 (tp53): c.77_80delinsaagaacgt (p.leu26fs), приводящая к формированию синдрома Ли – Фраумени (группа редких наследственных опухолевых заболеваний). Заключение. Впервые у пациентки (тувинский этнос) с ранним началом РМЖ и отягощенным онкологическим анамнезом описан вариант гена tp53 (rs1555526933), который может быть связан с синдромом наследственной предрасположенности к РМЖ, включая синдром Ли – Фраумени. Ключевые слова: наследственные мутации, рак молочной железы, малые народы России, этносы,

BACKGROUND:Germline alterations in BRCA1, BRCA2, and other genes are responsible for early-onset breast cancer. However, 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 significance are unknown. This study aimed to reclassify variant of unknown significance (VUS) or novel variants by using the ActiveDriveDB database that annotates variants through the lens of sites of post-translational modifications (PTM).METHODS:Our study included thirty-eighth young Buryat BC patients, belonging to the Mongoloid race and anthropologically to the Central Asia. Genomic DNA was extracted from the peripheral blood lymphocytes using the phenol/chloroform method. DNA library were prepared using the Hereditary Cancer SolutionTM kit (Sophia GENETICS, Switzerland) to cover 27 genes, such as 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 x 150 bp) was conducted using NextSeq 500 system (Illumina, USA).RESULTS:We re-examined 135 rare variants (41 VUS, 25 conflicting, 64 benign and 5 new variants). We identified 10 out of 135 (7.4%) mutations that affected the sites of post-translational modification in proteins. Of 135 rare mutations, 1 benign variant was reclassified as network-rewiring - motif loss mutation, 3 VUS and 1 new variant were reclassified as distal PTM- mutations, 2 new and 1 benign variant were classified as proximal PTM- mutations and 1 benign and 1 conflicting variant were classified as direct PTM- mutations.CONCLUSIONS:For the first time, 7.4% (10 out of 135) of mutations that affected the sites of post-translational modification in proteins were identified among early-onset breast cancer women of Mongoloid origin.

Introduction Variants in the BRCA1/2 genes are responsible for familial breast cancer. Numerous studies showed a different spectrum of BRCA variants among breast cancer patients of different Ethnicity origin. In the available literature, no previous research has focused on breast cancer-associated variants among the Khakass people (the indigenous people of the Russian Federation). Methods Twenty-six Khakass breast cancer patients were enrolled in the study. Genomic DNA was isolated from blood samples and used to prepare libraries using a Hereditary Cancer Solution kit. Next-generation sequencing (NGS) was performed using the MiSeq System (Illumina, USA). Results In our study, 12% of patients (3/26) carried a single pathogenic variant; 54% of patients (14/26) carried variants of uncertain significance (VUS) or conflicting variants; and 35% of patients (9/26) did not carry any clinically significant variants. Germline pathogenic variant in the ATM gene (rs780619951, NC_000011.10:g.108259022C > T) was identified in two unrelated patients with a family history of cancer (7.6%, 2/26). The pathogenic truncating variant in the ATM gene (p. R805* or c.2413C > T) leads to the nonfunctional version of the protein. This variant has been earlier reported in individuals with a family history of breast cancer. Conclusions Our pilot study describes the germline variant in the ATM gene associated with breast cancer in Khakass women of North Asia.

Objective: Develop a new organizational form of a personalized approach to assign a target therapy to the patients with metastatic nephrocellular cancer concerning its clinical and economic effectiveness.Methods: The data by cancer register of the Primorsky region were used. 446 patients are included in the register, it allowed to estimate clinical-economic effectiveness of the target therapy by studying 88 cases.Results: 5 medicines were used: sunitrib, soraphenib, bevazizumab, everolimus and pazopanib. The control of the progress of the disease and the toxicity covered 44,3% of the patients. The toxicity of the 3–4th levels were registered during the treatment by inhibitors tyrozinkinaz. The target line therapy increased expenditures by 10% and allowed to increase overall survivability to 42 months.Conclusion: An electronic register of the patients provides monitoring, optimizes expenditures and increases the availability of the target therapy up to 19,7%. Sequential therapy is reasonable and provides the increase of the overall patients’ survivability.

In accordance with the Asian BRCA Consortium data, there is a significant difference in incidence rate of breast cancer depending on age, as well as spectrum and prevalence of BRCA1/2 mutations between Mongoloid (East Asian) and Caucasoid (European) people. However, European strategies to identify familial BC are still applied to the Asian population, including Russian Mongoloids (Khakas, Buryats, Tyvans and Yakuts and others). The main purpose of the study was to identify molecular changes associated with hereditary BC in Russian Mongoloid BC patients (Buryats). Thirty-nine patients were included in the study. Genomic DNA extracted from lymphocytes was used to prepare DNA-libraries. Target sequencing was designed to cover 27 genes, such as ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2 and others. Paired-end sequencing (2 × 150 bp) was conducted on a NextSeq 500 system (Illumina, USA). Three pathogenic mutations in non-BRCA genes were found (prevalence of 8%). The pathogenic mutations were found in the RAD51D and PTEN genes. The pathogenic variant in the RAD51D gene (rs137886232, NC_000017.10:g.33428366G>A, p.R141X) was observed in two unrelated individuals aged under 40. One of these patients had a family history of late-onset stomach cancer in second-degree relatives. The pathogenic mutation in the PTEN gene (rs786201044, NC_000010.10:g.89692922T>C, p.C136R) was observed in a 38 years old breast cancer patient with no family history. In our study, we first describe pathogenic mutations in RAD51D and PTEN genes found in young Buryat patients.

© Коллектив авторов, 2019 На протяжении последних трех десятилетий в струк­ туре онкологической заболеваемости женского населения России лидирует рак молочной железы (РМЖ) [1]. По дан­ ным 2013 г., его удельный вес в Российской Федерации (РФ) составил 20,9%, в Сибири — 19,7%, в Республике Бу­ рятия (РБ) — 20,4%. Сохранилась тенденция дальнейшего роста показателей: за 4 года (2013—2016 гг.) прирост забо­ леваемости РМЖ в РФ составил 8,1% при среднегодовом темпе прироста 2,6%, в Сибирском федеральном округе (ФО) — 10,6 и 3,4%, в РБ — 6,3 и 2,1% соответственно [2, 3]. В РБ РМЖ является самым распространенным злокаче­ ственным новообразованием (ЗНО) среди женщин, однако республика характеризуется сравнительно низкими показа­ телями заболеваемости РМЖ. Одним из позитивных фак­ торов подобного положения вещей, возможно, является эт­ ническая неоднородность населения. В настоящее время в РБ живут представители более 167 национальностей и на­ родностей. Русское население Бурятии начало складывать­ ся с середины XVII века, в советский период наблюдалось увеличение доли русских с 61,6% (1925) до 69,9% (1989) и снижение доли бурят с 33,7 до 27,8% соответственно. За пе­ риод с 1989 по 2010 г. происходил обратный процесс: до­ ля русских снизилась с 69,9% (726,2 тыс. человек) до 67,8% (665,5 тыс. человек). Тем не менее это самая многочислен­ https://doi.org/10.17116/profmed20192202162

To date, there are a limited number of reports on inherited gene mutations associated with breast cancer (BC) among Mongoloid indigenous people in Russia. The present study aimed at identifying the BC-associated genes in 26 Russian Mongoloid BC patients (Buryats, Tuvinians and others). The median age of the patients at the time of breast cancer diagnosis was 41 years (range 25–51 years). Genomic DNA isolated from blood samples was 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). Next-generation sequencing (NGS) was performed on an Illumina NextSeq 500 System (Illumina, USA). In our study, we found 1 Indel and 11 SNPs that passed filters during variant calling. We identified a highly pathogenic germline rs483353122 (c.8208_8209insAG, p.Leu2737Serfs*2) in the BRCA2 gene in six unrelated Tuvinian Mongol BC patients. We also identified a likely damaging germline rs35352891 in the MUTYH gene (c.1118C>T, p.Ala373Val) in one Buryat Mongol BC patient. Other SNPs were classified as variants of uncertain significance. To the best of our knowledge, this report is the first to describe the highly pathogenic variant in the BRCA2 gene (rs483353122) and the likely damaging germline variant in the MUTYH gene (rs35352891) in Russian Mongoloid BC patients with young-onset and/or bilateral and/or familial BC. Further studies are therefore necessary to evaluate the contributions of novel sequence variants to hereditary BC.

The breast cancer is one of main localizations among malignant tumors in women of the Siberian Federal District. In the structure of morbidity it holds first place with such percentage as 20.4% and index of morbidity makes up to 51.2 per 100 000 of female population. The territories with increased and decreased risk are established. The features of prevalence of disease in a certain degree are conditioned by differences in demographic characteristics of populations. The indices of life-span, birth-rate in fertile age and divorce rate effect the level of morbidity of breast cancer in population.

Background. There is a global increase in incidence and mortality from kidney cancer. Kidney cancer is one of the most common oncological urology pathologies. Objective: to analyze the mortality data from kidney cancer in the Primorsky Krai population. Materials and methods . To study the epidemiology of kidney cancer, we used the database of incidence and mortality from kidney cancer of the Primorsky Krai population, formed in the laboratory of epidemiology of the Cancer Research Institute, Tomsk National Research Medical Center, based on data from the cancer register of Primorsky Regional Clinical Oncologic Dispensary and data of the Federal state statistics service. Calculations and analysis of indicators were carried out according to standard methods used in oncoepidemiological studies. Results. The kidney cancer mortality in males andfemales residing in Primorsky Krai was analyzed for the period 2001 to 2015. The highest kidney cancer mortality rate was observed in patients aged 70—74 years. The average age of patients died from kidney cancer was the sixth decade of their life. The life expectancy for men was shorter by 4.8 years than that for women (p <0.05). The kidney cancer mortality is expected to increase by 7.5 % in men and decrease by 6.8 % in women in 2020, being 7.2 ± 0.7 °/ 0000 (r 2 = 0.4) and 2.7 ± 1.4 °/ 0000 (r 2 = 0.02), respectively. No statistically significant differences in the rise of kidney cancer mortality rates compared to the rise in the kidney cancer incidence rates were found (p >0.05), therefore, kidney cancer mortality stabilization was observed. Conclusion. Against the background rising the incidence, the mortality of patients with kidney cancer in population of the Primorsky Krai tends to decline.

The purpose of the study was to estimate the medical care for cancer patients in the Amur region from 1999 to 2014. Material and methods. The study was based on cancer register data collected at the Oncology Dispensary of Amur region and covered the period 1999 to 2014. Results. Breast cancer is the most common cancer in women of the Amur region, accounting for 20.8 % of all cancer cases. In 2013, the breast cancer incidence rate was 52.8 per 100,000. The incidence rate for breast cancer increased by 36.4 % from 2003 to 2013, the overall rise being 2.2 %. The mortality rate decreased from 20.3 % in 2003 to 17.3 % in 2014. Cancer care in rural areas of the Amur region is worse than in Blagoveshchensk, which is the regional administrative center. The one-year mortality rate in rural areas is 1.3 times higher than that in the city. The one-year mortality rate is 1.3 times higher in rural areas than in the city, and is 1.2 times higher in the Amur region than in the Russian Federation. Conclusion. Appropriate treatment and prevention measures are recommended for further improvement of medical care for breast cancer patients in the Amur region.

The article reviews the rates of incidence, late diagnosis and mortality from kidney cancer in Primorsky Krai. The authors address the issues of improving primary and specialized medical care by introducing a three-level health care system and restructuring of hospital beds. They propose a new medical technology for assessing the individual risk of kidney cancer and present a program of measures and organizational modules for prevention, early diagnosis and reduction of mortality from kidney cancer.

The breast cancer is one of main localizations among malignant tumors in women of the Siberian Federal District. In the structure of morbidity it holds first place with such percentage as 20.4% and index of morbidity makes up to 51.2 per 100 000 of female population. The territories with increased and decreased risk are established. The features of prevalence of disease in a certain degree are conditioned by differences in demographic characteristics of populations. The indices of life-span, birth-rate in fertile age and divorce rate effect the level of morbidity of breast cancer in population.

BACKGROUND: The BRCA1 mutations that are endemic to the Slavic population of Russia have not been identified among indigenous peoples, including the Buryats, Tuvinians and Altaians with hereditary breast cancer.OBJECTIVE: This study was aimed to identify the mutations that are responsible for the occurrence of hereditary breast cancer in the indigenous population of the Republic of Buryatia.METHODS: Mutations in the BRCA1 gene were identified in blood samples by Sanger-based sequencing.RESULTS: We identified 11 polymorphisms (10 SNPs and 1 Indel) and 6 new unclassified sequence variants in the BRCA1 gene. In our study three new sequence variants (c. 321T>A, c. 366T>A, c. 4357+2T>A) were found in position of previously described polymorphisms in dbSNPs: rs80357544 (c. 321delT), rs190900046 (c.366T>G), and rs80358152 (c. 4357+ 2T>C), respectively. Other three new sequence variants (c. 3605A>G, c. 1998A>C, and c. 80+13A>C) have not been previously described in dbSNP, BIC and Human Gene Mutation Databases.CONCLUSIONS: We described six new sequence variants that have never been published in the literature or databases. Further studies are required to confirm the impact of new sequence variants on the risk of breast cancer in the Buryat Mongol population.