The search for microRNAs potentially involved in the selfrenewal maintaining of laboratory rat pluripotent stem cells

Self-renewal of cultured pluripotent stem cells is a complex process, which includes multiple functional and regulatory levels. Transcription factors, their target genes, chromatin modifiers, signaling pathways, and regulatory noncoding RNAs are involved in the maintaining of self-renewal. Studies of molecular and genetic bases of maintaining self-renewal and pluripotency in cultured mammalian cells are important to understand processes in preimplantation embryogenesis and to develop efficient techniques to obtain pluripotent stem cell lines for experimental biology and medicine. MicroRNAs (miRNAs) play an important role in pluripotency maintaining and reprogramming. However, involvement of this class of noncoding RNAs and functions of individual molecules are poorly studied. The goal of this study was the search for the miRNAs potentially involved in the pluripotency maintaining and reprogramming of Rattus norvegicus cells. We analyzed the expression of miRNAs in rat embryonic stem cells, induced pluripotent stem cells and embryonic fibroblasts using bioinformatic methods and data obtained with next generation sequencing. The analysis of differential expression between groups of rat pluripotent cells and fibroblasts, and the analysis of experimentally confirmed target genes of differentially expressed known rat miRNAs revealed novel potential players of pluripotency maintaining and reprogramming processes. In addition, novel members of these processes were revealed among novel rat miRNAs. The use of bioinformatic and systems biology approaches is the first step, which is necessary for choosing candidates for the subsequent experimental studies. The results obtained substantially improve our understanding of the self-renewal regulation system of the laboratory rat, a popular biomedical object, and our knowledge about the system in mammals

СПЕКТР МУТАЦИЙ ГЕНА BRCA1 У БОЛЬНЫХ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ В МОЛОДОМ ВОЗРАСТЕ В РОССИИ

Aim of the study. Aim of the study was to estimate the occurrence of pathogenic mutations in the BRCA1 gene in Russian breast cancer patients.Material and methods. Complete coding sequence of the BRCA1 gene of 445 early onset  breast cancer patients (under 40 years) from Novosibirsk region (Russia) were analyzed by  targeted Next Generation Sequencing (NGS) using Ion Torrent platform. Results. Forty (9%) carriers of various pathogenic mutations were revealed. Thirty five (7,9%) patients  carried 5382insC mutation, described earlier as a founder mutation for Slavic population.  Five (1.1%) patients carried various pathogenic mutations, namely C61G, 462delCC, E143X,  4153delA, and IVS18+1G>T. Besides, 29 genetic variants with no clinical significance or with  unknown clinical significance were detected in BRCA1 gene among 445 early onset breast  cancer patients. Conclusions. Data on the frequency of genetic variations in the BRCA1 gene among early onset breast cancer patients in the Novosibirsk Region (Russia) were  obtained. Proportion of the 5382insC mutation is 87.5% of all pathogenic mutations in the BRCA1 gene found in patients.Цель исследования – оценить частоту встречаемости патогенных мутаций в BRCA1 гене у женщин с раком молочной железы, проживающих в России.Материал и методы. Проведён анализ полной кодирующей части гена BRCA1 у 445 больных раком молочной  железы на ранней стадии (возраст больных до 40 лет), проживающих в Новосибирской области (Россия), с  помощью метода таргетного секвенирования на платформе Ion Torrent. Результаты. Выявлено 40 (9 %)  носительниц различных патогенных мутаций. У 35 (7,9 %) пациенток обнаружена мутация 5382insC, описанная  ранее как «мутация-основателя» в славянской популяции. У 5 (1,1 %) пациенток были выявлены  другие различные патогенные мутации, а именно C61G, 462delCC, E143X, 4153delA и IVS18 + 1G> T. Кроме  того, 29 генетических вариантов с отсутствующей или неясной клинической значимостью были обнаружены в  гене BRCA1 у 445 больных раком молочной железы на ранней стадии. Выводы. Получены данные о частоте  генетических вариаций гена BRCA1 у больных раком молочной железы на ранней стадии, проживающих в  Новосибирской области (Россия). Доля мутации 5382insC составляет 87,5 % от всех патогенных мутаций в гене BRCA1, обнаруженных у пациенток

The spectrum of BRCA1 gene mutations in early onset breast cancer patients from Russia

Aim of the study. Aim of the study was to estimate the occurrence of pathogenic mutations in the BRCA1 gene in Russian breast cancer patients.Material and methods. Complete coding sequence of the BRCA1 gene of 445 early onset  breast cancer patients (under 40 years) from Novosibirsk region (Russia) were analyzed by  targeted Next Generation Sequencing (NGS) using Ion Torrent platform. Results. Forty (9%) carriers of various pathogenic mutations were revealed. Thirty five (7,9%) patients  carried 5382insC mutation, described earlier as a founder mutation for Slavic population.  Five (1.1%) patients carried various pathogenic mutations, namely C61G, 462delCC, E143X,  4153delA, and IVS18+1G>T. Besides, 29 genetic variants with no clinical significance or with  unknown clinical significance were detected in BRCA1 gene among 445 early onset breast  cancer patients. Conclusions. Data on the frequency of genetic variations in the BRCA1 gene among early onset breast cancer patients in the Novosibirsk Region (Russia) were  obtained. Proportion of the 5382insC mutation is 87.5% of all pathogenic mutations in the BRCA1 gene found in patients