BRCA1/2 genes mutations frequency in patients with various histological types of ovarian cancer (data for South of Russia).

person Natalya N. Timoshkina National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation info_outline Natalya N. Timoshkina, Natalia A. Petrusenko, Madina A. Gappoeva, Sergey E. Kavitskiy, Maria A. Cherkes, Ekaterina V. Verenikina, Denis S. Kutilin, Dmitry Yu. Gvaldin

Authors person Natalya N. Timoshkina National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation info_outline Natalya N. Timoshkina, Natalia A. Petrusenko, Madina A. Gappoeva, Sergey E. Kavitskiy, Maria A. Cherkes, Ekaterina V. Verenikina, Denis S. Kutilin, Dmitry Yu. Gvaldin Organizations National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation Abstract Disclosures Research Funding Other Background: About 10-15% of malignant ovarian tumors (OC) are associated with hereditary diseases, and about 65-85% of hereditary OC have a mutation in BRCA1/2 genes. The aim of the study was to analyze BRCA1/2 genes hereditary mutation spectrum in patients in the South of Russia diagnosed with OC. Methods: We used EDTA venous blood and FFPE-blocks of 324 patients with histologically verified epithelial OC (T1-3cNx-1Mx-1, stage I-IV). BRCA1 gene mutations (185delAG, 300T > C, 2080delA, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT) and BRCA2 gene mutations (6174delT) were determined by real-time PCR. Results: The most common types of OC were poorly differentiated serous carcinoma (high degree of malignancy) - 75.6%, well-differentiated serous carcinoma (low degree of malignancy) - 13%, mucinous tumors - 2.8%, endometrioid tumors - 4.3%, clear cell adenocarcinomas - 4.3%. BRCA1/2 genes mutations were found in 52 (16%) patients with OC. The frequency of detected BRCA1/2 genes mutations was: 5382insC - 53.8%, 4153 delA - 9.6%, 300T > G - 21.2%, 2080delA - 7.7%, 185delAG - 3.8%, 6174delT - 3.8%. 3819delGTAAA and 3875delGTCT mutations were not found in the BRCA1 gene. All carriers were confirmed to have the same mutations in the tumor. There were no cases of sporadic changes in BRCA1/2. BRCA1 mutation carriers prevailed in the group of high-grade serous carcinoma patients (11.1%), where all cases of BRCA2 gene mutations were identified. In the group of low-grade serous carcinoma patients, the mutation rate was 1.5%, in the endometrioid adenocarcinomas group - 0.6%, in the mixed epithelial tumors group - 2.8%. In the group of patients with mucinous tumors, mutations were not detected. Conclusions: Thus, frequency of BRCA1/2 gene mutations in OC patients living in the South of Russia was 16.0%. Distribution of mutation types in the BRCA1 gene, with a predominance of 5382insC (53.8%) and 300T > G (21.2%), corresponded to their occurrence ratio in the European populations. BRCA1/2 gene mutations were registered more often in the group of high-grade serous carcinoma patients.