Hereditary prostate cancer has special position due to young-age evolution, high risk of metastasis poor prognosis. The target of our study and practical work is an organization of a screening study to identify patients with germline mutations, which are leading to prostate cancer. As known, the relatives of patients with penetrant mutations in the BRCA 1/2, ATM, CHEK2, PALB2, RAD50, MSH2, MSH6 and another genes are at increased risk of developing prostate cancer.
This work is based on the analysis of results of molecular genetic testing of blood by sequencing of the “new generation” NGS of 161 female patients with germline mutations.
Mutations in the BRCA1 gene were detected in 105 patients, 14 patient has mutation in the BRCA 2 gene, in 4 in the CDKN2A gene, in 3 in the CHEK2 gene, in 3 in the ATM gene, in 2 in the AKT1 gene, in 2 in the CDH1 gene, in 2 in the gene FANCI, 1 in the APK gene, 1 in the ATR gene, 1 in the BAP1 gene, 1 in the BUB1 gene, 1 in the EPCAM gene, 1 in the MLH1 gene, 1 in the MLH3 gene, 3 in the MSH6 gene, 2 in the PULB2 gene, 1 in the POLD1 gene, 3 in the POLE gene, 1 in the PPM1D gene, 3 in the RAD50 gene, 1 in the RAD51D gene, 1 in the SMAD4 gene, 1 in the STK11 gene, 1 in the TP53 gene, in 1 in the CDK12 gene, in 1 in the ATM gene. After determining the mutations, each patient was consulted by a geneticist. A genealogy was compiled for each, identified relatives for conducting examinations. Sanger sequencing determines the specific pathogenic mutations characteristic of the identified patient mutations. These pathogenic mutations are characteristic of the identified mutations of the patient. When a penetrant mutation is detected, the proband is assigned a set of measures for the prevention and early diagnosis of prostate cancer.
The study is critical to optimizing prostate cancer screening approaches. Considering all capability, we suggest the early approach to prostate cancer screening for men with germinative mutation in a known gene. After that, based on the data of certain mutations specific mutations were determined in the patient's relatives. The study revealed healthy carriers of pathogenic mutations. The frequency of determining pathogenic mutations in the genes in question was determined. The early detection of prostate cancer were organization for patient with with pathogenic mutations.