ANALYSIS OF HERMINAL MUTATIONS IN ONCOGENES AND TUMOR SUPPRESSOR GENES IN WOMEN WITH MULTIPLE PRIMARY MALIGNANT NEOPLASMS

DOI: https://doi.org/10.29296/24999490-2020-02-10

A.V. Savkova(1), A.V. Gerasimov(2), G.V. Vasiliev(3), S.E. Krasilnikov(2), L.F. Gulyaeva(1), V.E. Voitsitsky(2) 1-Federal Research Center of Fundamental and Translational Medicine», Timakova street, 2, Novosibirsk, 630117, Russian Federation; 2-Novosibirsk Regional Clinical Oncological Dispensary, Plakhotnogo street, 2, Novosibirsk, 630108, Russian Federation; 3-Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Lavrenteva Avenue, 10, Novosibirsk, 630090, Russian Federation E-mail: [email protected]

Introduction. Multiple primary malignant neoplasms (MPMN) most often develop in individuals with a hereditary predisposition to oncological diseases. There are inherited allelic variants of oncogenes, tumor suppressor genes and their combinations which disrupt the functional activity of the corresponding proteins. This leads to the development of certain tumors and is clinically manifested as familial oncological syndromes. Materials and methods. Fifty key genes associated with carcinogenesis were sequenced for 8 women, developed MPMN and have a family tumor history. Results. A total of 26 polymorphic variants were identified in 18 genes. Ten of them are located in introns, one - in the regulatory region of the gene, ten of them are silent-mutations, five – are missense-mutations. Each patient has from 9 to 17 such variants. Probably the polymorphism RET rs1800863 in the existing genomic context in Patient № 1 predetermined the development of medullary thyroid cancer in her and her daughter. Family of patient №2 shows a picture typical of Li-Fraumeni-like syndrome. We assume that due to either the single homozygous TP53 rs1800372 polymorphism, or its combination with TP53 rs1042522 polymorphism, determines the presence of Li-Fraumeni-like syndrome in this family. Conclusion. The frequency of rs55986963, rs1050171, rs12628 polymorphisms in the sample exceeds that in the population. It is necessary to expand the sample at the expense of MPMN-patients and healthy women for further discussion
Keywords: 
multiple primary malignant neoplasms, inherited oncological syndrome, genetic analysis, oncogenes, tumor suppressor genes

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