Brieieva O. Genome instability in peripheral blood lymphocytes and endometrial carcinoma cells of patients with a family history of cancer

The dissertation is devoted to the study of the genome instability parameters in endometrial cancer (ЕС) patients on the basis of identifying specific molecular genetic changes in peripheral blood lymphocytes (PBL) and tumor cells and finding their relationship with the family history of cancer and clinical characteristics of patients. For the first time, it was found that PBL of EC patients is characterized by increased genome instability in terms of high level of baseline DNA damage, increased sensitivity to bleomycin and 4-hydroxyestradiol and reduced DNA repair efficiency of induced DNA damage compared to lymphocytes of healthy donors. For the first time, higher levels of baseline DNA damage were detected in tumor cells of EC patients with a family history of cancer than in cells of sporadic endometrial tumors. It is shown that the presence of a family history of cancer in EC patients is associated with a more pronounced decrease in repair efficiency of DNA damage in PBL induced by bleomycin and 4-hydroxyestradiol, compared to patients with sporadic tumors. It was determined that the frequency of detection of MMR-deficient tumors and tumors with high expression of c-Myc protein was higher in the group of EC patients with a family history of cancer compared with the group of patients with sporadic tumors. A correlation (r=0.61; p=0.03) was found between the efficiency of repair of bleomycin-induced DNA damage in the PBL of EC patients and the expression of MSH2 protein in carcinoma, which indicates the possible prospects of using PBL as extra tumor markers that reflect the state of repair systems in tumor cells. In endometrial tumors with a low degree of differentiation and deep invasion of the myometrium amplification and high expression of oncogenes Her-2/neu and c-MYC were found, which allows to consider them as potential markers that can be used to identify categories of EC patients with aggressive disease.