The hereditary ovarian cancer: role of candidate genes in disease pathogenesis

A significant number of ovarian malignancies are hereditary (up to 30% of all neoplasms result from a high genetic predisposition). At least 16 candidate genes for hereditary ovarian cancer are known, and with the introduction and widespread use of genome-wide sequencing, an increasing number of genes and genetic variants are potentially involved in the pathogenesis of familial forms of the disease, although the contribution of these genes to the development of hereditary ovarian cancer . The detection of specific mutations in a number of ovarian cancer candidate genes in healthy women can justify not only more intensive and personalized surveillance programs, chemoprophylactic approaches and / or preventive operations, but also can provide fundamental knowledge about the pathogenesis of tumor development. This article describes the clinical features of hereditary ovarian cancer due to mutations in the key candidate genes (BRCA1, BRCA2, TP53, BARD1, CHEK2, RAD51, PALB2). The main types of mutations in BRCA - associated ovarian cancer, age-related features and survival rates are described. It was shown that the majority (approximately 65-85%) of hereditary ovarian tumors account for germline mutations in the BRCA1 and BRCA2 genes. It is believed that mutations in these genes lead primarily to gynecological oncological diseases in estrogen-sensitive target organs, however, according to some reports, there is also the likelihood of cancer of the stomach, colon, endometrium, pancreas, skin melanoma, bladder, head and neck tumors. Approximately 6% of hereditary OC is accounted for by germline mutations of the BARD1, BRIP1, CHEK, MRE11A, MSH6, NBN, PALB2, RAD50, RAD51C and TP53 genes, the protein products of which are involved in the restoration of homologous recombination. Medium and low penetrant genes individually carry only minimal risk, but due to the multiplicative and / or cumulative effects, they can cause a relatively high risk for carriers. The article describes in detail the oncogenesis of ovarian cancer due to a mutation in the genes for the restoration of the mismatch MMR - Lynch syndrome, which is the second leading cause of hereditary ovarian cancer and makes up from 2% to 15% of all cases of the disease. Other proteins encoded by the RAD51, RAD50, ATM, MRE11 and PALB2 genes that interact with the products of the BRCA1 / 2 genes in the mechanism of homologous recombination repair are also described in detail

наследственный рак яичников, мутации BRCA1/BRCA2, синдром Линча, анемия Фанкони, ТР53, hereditary ovarian cancer, BRCA1/BRCA2 mutations, Lynch syndrome, Fanconi anemia, ТР53