Germinal mutations landscape, which is responsible for cancer predisposition in multinational Republic of Bashkortostan.

Abstract

e22504 Background: In oncology hereditary forms of malignant neoplasms occupy a special position due to the frequent cases at a young age and poor prognostic factors. The aim of this work is to determine in cancer patients germinal mutations which are responsible for cancer predisposition. Methods: The study included patients with burdened family history or those with a manifestation of malignant neoplasm at a young age residing on the territory of multinational Republic of Bashkortostan. The patients were diagnosed with one of these diseases: breast cancer, prostate cancer, pancreatic cancer, gastric cancer, colon cancer. The study is based on analyses of the molecular genetic blood testing n cancer patients using real-time polymerase chain reaction (PCR) for detection of 8 widely spread mutations among Russian population: in BRCA 1 gene were detected such mutations as 185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, 300T>G, 2080delA; in gene BRCA 2 - 6174delT. Blood samples of the rest amount of patients which proved no mutations by PCR method was tested by the “next-generation” sequencing method (NGS). Results: The results of the study showed territorial features of presence of germinal mutations of Russian multinational region. The results of the study aimed to reveal the spectrum and frequency of gene mutations characteristic for the particular region: BRCA 1 - c.5266dupC, c.3143delG, c.5161C>T, c.5382 insC, c.3819delGTAAA, c.300T>G, c.5136G>A, 185delAG, 4153delA, 2080delA; BRCA 2 - c.6621_6622del, с.39-1_39delGA, c.961_962insAA; CHEK2 - c.470T>C, c.444+1G>A; PALB2 - c.1592delT; RAD50 - c.2157delA; MLH1 - c.1637A>G; MSH6 - c.2554_2556del; STK11 - c.368A>G; MSH2 - c.815C>T. According to the mutation detection the patient consulted a geneticist for making a genealogic tree for future molecular genetics exam. Hereinafter the control group included relatives of patients who remain potential carriers of pathogenic mutations of the proband using Sanger sequencing method. When penetrate mutations are identified in healthy population, a set of measures is taken to prevent and early diagnose malignant tumors. Conclusions: The results of the study showed features of presence of each detected mutation which is characteristic for south-eastern part of the Russian multinational region. This study plays an important role in the process of optimization of screening of germinal mutation carriers among healthy population and as a result it helps to conduct prophylactic measures to early diagnose malignant neoplasms.

Experience with olaparib in the treatment of BRCA-associated tumors in real clinical practice. Observational study

“…ARP-ингибиторы [поли(АДФ-рибоза)-полимеразы]класс препаратов, влияющих на механизмы репарации одноцепочечных разрывов ДНК, что фатально для клеток, имеющих дефицит системы репарации двухцепочечных разрывов. Последнее характерно для генетической патологии в генах BRCA1 и BRCA2, имеющей наследственный характер [1,2]. Достаточно важным предполагается тот факт, что в группе здоровых носителей герминальных мутаций в генах BRCA1/2 риск возникновения злокачественных новообразований остается высоким, и необходимы мероприятия по скринингу [3].…”