The copy number variations of genes regulating mitochondrial function in benign and malignant uterine body neoplasms

Purpose of the study. To study changes in the copy number of genes whose products are involved in maintaining the structure and function of mitochondria in tissues of benign neoplasms and endometrioid adenocarcinoma (EA) of the uterine body of varying degrees of differentiation.

Materials and methods. The study utilized tumor tissue and normal uterine tissue from 42 patients with endometrioid adenocarcinoma (EA) and 15 patients with uterine fibroids. The tumor burden in the EA patients was between stages Ia and Ib, and neoadjuvant treatment was not administered. DNA was isolated from tumor and normal uterine tissue fragments using phenol-chloroform extraction, and relative gene copy numbers were determined using real-time PCR (real-time qPCR). Statistical analysis was performed using the Mann-Whitney U-test with a Bonferroni correction.

Results. In patients with EA G1, a decrease in the copy number of nuclear and mitochondrial genes was observed (MT-CO1 = 0.5, mtTFB = 0.4, mtSSB = 0.6, MT-RNR2 = 0.3, NRF1 = 0.4) (p < 0.005) and an increase in the copy number of MGME1 (2.4) (p < 0.005). In patients with EA G2, a picture similar to G1 is observed: a decrease in the copy number of the genes MT-CO1; mtTFB, MT-RNR2 and NRF1 (p < 0.005), except for mtSSB. An increase in the copy number of MGME1 (3.1) and POLRMT (1.8) (p < 0.005) was also recorded. In patients with EA G3, the most pronounced decrease in the copy number of mtSSB and MT-RNR2 by 5.0 times relative to normal tissue was found, as well as a decrease in the copy number of MGME1 by 3.3 times, which is the opposite of the results in G1/G2.

Conclusion. Significant differences in the copy number of genes involved in mitochondrial function were identified between benign uterine tissues and endometrioid adenocarcinoma. The most prominent alterations included reduced copy numbers of key mitochondrial genes (MT-CO1 and MT-RNR2), the nuclear gene mtSSB, and aberrant MGME1 copy number changes in tumor tissues. These findings provide new insights into the molecular mechanisms underlying endometrioid adenocarcinoma development and may contribute to the identification of potential diagnostic and prognostic biomarkers.

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