2658-6533Research Results in Biomedicine2658-653310.18413/2658-6533-2024-10-4-0-13589Genetics<strong>Ovarian cancer: the significant of gene methylation in carcinogenesis (review)</strong><br /> &nbsp;<strong>Ovarian cancer: the significant of gene methylation in carcinogenesis (review)</strong><br /> &nbsp;AndreevaEkaterina A.AndreevaEkaterina A.ekaterinabiology@yandex.ruMingazhevaElvira T.MingazhevaElvira T.elvira.f91@mail.ruFaiskhanovaRania R.FaiskhanovaRania R.rancho111@mail.ruValovaYana V.ValovaYana V.Q.juk@yandex.ruFedorovaYulia Yu.FedorovaYulia Yu.fedorova-y@yandex.ruNurgalievaAlfiya Kh.NurgalievaAlfiya Kh.alfiyakh83@gmail.comSakaevaDina D.SakaevaDina D.D_sakaeva@mail.ruKhusnutdinovaElza K.KhusnutdinovaElza K.elzakh@mail.ruProkofievaDarya S.ProkofievaDarya S.dager-glaid@yandex.ru202410400

Background: Epigenetic regulation of genes plays an important role in the development of ovarian cancer. One of these mechanisms is DNA methylation of tumor suppressor genes and oncogenes. A detailed study of methylation can serve as an important step towards improving the methods of early screening for OC. The aim of the study: Based on the study of modern literature data, to consider the role of DNA methylation in the pathogenesis of ovarian cancer and evaluate its contribution to the development of this disease. Materials and methods: Literature data were analyzed using the following keywords: DNA methylation, ovarian cancer, epigenetic regulation, epidemiology of ovarian cancer. Results: According to the literature data, hypermethylation of promoters of suppressor genes or, conversely, hypomethylation of oncogenes is noted in oncological diseases. Thus, it has been established that hypermethylation of the promoters of the OPCML, PAX1, CDH1, HOXA9, HIC1, MLH1 genes is often observed in ovarian cancer. Methylation of the HIST1H2BB, MAGI2, HOXA10 and HOXA11, LAMA3, ESR1, TNF, MUC1 and FOXO1 genes has an important diagnostic and/or prognostic value. The methylation of miRNA genes plays a special role in the progression of ovarian cancer. Conclusion: In contrast to genetic changes, DNA methylation is a reversible process, which is very promising for the development of new therapeutic approaches and for early diagnosis of the disease, where hypermethylation of gene promoters can serve as biomarkers. Numerous studies support the important role of methylation tumor suppressor genes and various microRNAs in oncogenesis, and predisposes to the development of a field of research aimed at deciphering the human epigenome. Understanding the mechanisms of epigenetic regulation of the development and course of cancer will contribute to the development of new diagnostic and prognostic methods and approaches for cancer treatment

Background: Epigenetic regulation of genes plays an important role in the development of ovarian cancer. One of these mechanisms is DNA methylation of tumor suppressor genes and oncogenes. A detailed study of methylation can serve as an important step towards improving the methods of early screening for OC. The aim of the study: Based on the study of modern literature data, to consider the role of DNA methylation in the pathogenesis of ovarian cancer and evaluate its contribution to the development of this disease. Materials and methods: Literature data were analyzed using the following keywords: DNA methylation, ovarian cancer, epigenetic regulation, epidemiology of ovarian cancer. Results: According to the literature data, hypermethylation of promoters of suppressor genes or, conversely, hypomethylation of oncogenes is noted in oncological diseases. Thus, it has been established that hypermethylation of the promoters of the OPCML, PAX1, CDH1, HOXA9, HIC1, MLH1 genes is often observed in ovarian cancer. Methylation of the HIST1H2BB, MAGI2, HOXA10 and HOXA11, LAMA3, ESR1, TNF, MUC1 and FOXO1 genes has an important diagnostic and/or prognostic value. The methylation of miRNA genes plays a special role in the progression of ovarian cancer. Conclusion: In contrast to genetic changes, DNA methylation is a reversible process, which is very promising for the development of new therapeutic approaches and for early diagnosis of the disease, where hypermethylation of gene promoters can serve as biomarkers. Numerous studies support the important role of methylation tumor suppressor genes and various microRNAs in oncogenesis, and predisposes to the development of a field of research aimed at deciphering the human epigenome. Understanding the mechanisms of epigenetic regulation of the development and course of cancer will contribute to the development of new diagnostic and prognostic methods and approaches for cancer treatment

hereditary ovarian cancerepigenetic regulationDNA methylation of tumor suppressor genesmethylation of microRNA geneshereditary ovarian cancerepigenetic regulationDNA methylation of tumor suppressor genesmethylation of microRNA genesСписок литературыGlobal cancer observatory [Internet] [cited 2023 Apr 30]. Available from: https://gco.iarc.fr/Croft PK, Sharma S, Godbole N, et al. Ovarian-cancer-associated extracellular vesicles: Microenvironmental regulation and potential clinical applications. Cells. 2021;10(9):2272. DOI: https://doi.org/10.3390/cells10092272Villert AB, Kolomiets LA, Yunusova NV, et al. Ascites as a subject of studies in ovarian cancer. Siberian journal of oncology. 2019;18(1):116-123. Russian. DOI: https://doi.org/10.21294/1814-4861-2019-18-1-116-123Kushlinsky NE, Stilidi IS, Ognerubov NA, et al. Ovarian cancer: basic and clinical research. M.: Prospect; 2021. Russian.Mullayanova LSh, Mullagaleeva EF, Vladimirova EI, et al. Assessment of the role of the new candidate gene KIR3DL1 in the pathogenesis of ovarian cancer based on the results of complete exom sequencing. Research&#39;n Practical Medicine Journal. 2019;6(S):199-200. Russian.Valova YV, Mingazheva ET, Prokofieva DS, et al. Ovarian cancer as part of hereditary cancer syndromes (review). Research Results in Biomedicine. 2021;7(4):330-362. Russian. DOI: https://doi.org/10.18413/2658-6533-2021-7-4-0-2Tikhomirova TE, Tyulyandina AS, Rumyantsev AA, et al. BRCA-associated ovarian cancer: a review of the current literature. Pelvic Surgery and Oncology. 2022;12(3):56-62. Russian. DOI: https://doi.org/10.17650/2686-9594-2022-12-3-56-62Faiskhanova RR, Sakaeva DD. Lynch syndrome as a manifestation of hereditary ovarian cancer: a case report of treatment of a patient with platinum-sensitive recurrent ovarian cancer. Medical Council. 2021;(4S):114-119. Russian. DOI: https://doi.org/10.21518/2079-701X-2021-4S-114-119Lipatov ON, Akhmetgareeva KT. The Role of Genetic Mutations in the Prevention of Malignant Tumours in a Healthy Population (A Review). Creative surgery and oncology. 2020;10(4):330-338. Russian. DOI: https://doi.org/10.24060/2076-3093-2020-10-4-330-338Cancer research UK [Internet] [cited 2023 Apr 30]. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer/risk-factors#heading-FourUrmancheeva AF, Kutusheva GF, Ulrikh EA. Ovarian tumors: clinic, diagnosis and treatment. St. Petersburg: N-L; 2012. Russian.Ohnishi K, Nakayama K, Ishikawa M, et al. Mucinous borderline ovarian tumors with BRAFV600E mutation may have low risk for progression to invasive carcinomas. Archives of Gynecology and Obstetrics. 2020;302(2):487-495. DOI: https://doi.org/10.1007/s00404-020-05638Lin DI, Killian JK, Venstrom JM, et al. Recurrent urothelial carcinoma-like FGFR3 genomic alterations in malignant Brenner tumors of the ovary. Modern Pathology. 2021;34(5):983-993. DOI: https://doi.org/10.1038/s41379-020-00699-1Klymenko Y, Nephew KP. Epigenetic crosstalk between the tumor microenvironment and ovarian cancer cells: a therapeutic road less traveled. Cancers. 2018;10(9):295. DOI: https://doi.org/10.3390/cancers10090295Singh A, Gupta S, Sachan M. Epigenetic biomarkers in the management of ovarian cancer: current prospectives. Frontiers in Cell and Developmental Biology. 2019;7:182. DOI: https://doi.org/10.3389/fcell.2019.0018216. Krebs J, Goldstein E, Kilpatrick S. Genes according to Lewin. Moscow: Laboratoriya znanij; 2022. Russian.17. Valle BL, Rodriguez-Torres S, Kuhn E, et al. HIST1H2BB and MAGI2 Methylation and Somatic Mutations as Precision Medicine Biomarkers for Diagnosis and Prognosis of High-grade Serous Ovarian Cancer. Cancer Prevention Research. 2020;13(9):783-794. DOI: https://doi.org/10.1158/1940-6207.CAPR-19-041218. Esenova ME, Payanidi YuG, Vinokurova SV, et al. Genetic and epigenetic profiling of the BRCA1 / 2 genes in solitary ovarian cancer and multiple primary ovarian tumors. Pelvic Surgery and Oncology. 2021;11(2):11-18. Russian. DOI: https://doi.org/10.17650/2686-9594-2021-11-2-11-18Kalachand RD, Stordal B, Madden S, et al. BRCA1 promoter methylation and clinical outcomes in ovarian cancer: an individual patient data meta-analysis. Journal of the National Cancer Institute. 2020;112(12):1190-1203. DOI: https://doi.org/10.1093/jnci/djaa070Kwon JS. Comments on: Peripheral blood BRCA1 methylation profiling to predict familial ovarian cancer. Journal of Gynecologic Oncology. 2021;32(2):e33. DOI: https://doi.org/10.3802/jgo.2021.32.e33Yan B, Yin F, Wang QI, et al. Integration and bioinformatics analysis of DNA‑methylated genes associated with drug resistance in ovarian cancer. Oncology Letters. 2016;12(1):157-166. DOI: https://doi.org/10.3892/ol.2016.4608Abramov PM, Vinokurova SV, Elkin DS. DNA methylation markers for diagnosis of serous ovarian cancer. Gynecologic Oncology. 2019;4:4-16. Russian.Qiao B, Zhang Z, Li Y. Association of MGMT promoter methylation with tumorigenesis features in patients with ovarian cancer: a systematic meta‐analysis. Molecular genetics &amp; genomic medicine. 2018;6(1):69-76. DOI: https://doi.org/10.1002/mgg3.349Antony J, Zanini E, Kelly Z, et al. The tumour suppressor OPCML promotes AXL inactivation by the phosphatase PTPRG in ovarian cancer. EMBO Reports. 2018;19(8):e45670. DOI: https://doi.org/10.15252/embr.201745670Dvorsk&aacute; D, Bran&yacute; D, Nagy B, et al. Aberrant methylation status of tumour suppressor genes in ovarian cancer tissue and paired plasma samples. International Journal of Molecular Sciences. 2019;20(17):4119. DOI: https://doi.org/10.3390/ijms20174119Maltseva LI, Kiselev VI, Poloznikov AA, et al. Effectiveness of chronic endometritis therapy with Epigallocatechin-3-gallate in women with reproductive dysfunction. Practical medicine. 2019;17(4):62-67. Russian. DOI: https://doi.org/10.32000/2072-1757-2019-4-62-67Singh A, Gupta S, Badarukhiya JA, et al. Detection of aberrant methylation of HOXA9 and HIC1 through multiplex MethyLight assay in serum DNA for the early detection of epithelial ovarian cancer. International Journal of Cancer. 2020;147(6):1740-1752. DOI: https://doi.org/10.1002/ijc.32984Tryakin AA, Fedyanin MYu, Tsukanov AS, et al. Microsatellite instability as a unique characteristic of tumors and a predictor of response to immune therapy. Malignant tumours. 2019;9(4):59-69. Russian. DOI: https://doi.org/10.18027/2224-5057-2019-9-4-59-69Shilpa V, Bhagat R, Premalata CS, et al. Microsatellite instability, promoter methylation and protein expression of the DNA mismatch repair genes in epithelial ovarian cancer. Genomics. 2014;104(4):257-263. DOI: https://doi.org/10.1016/j.ygeno.2014.08.016LAMA3 laminin subunit alpha 3 [Homo sapiens (human)] [Internet] [cited 2023 Apr 30]. Available from: https://www.ncbi.nlm.nih.gov/gene/3909Feng L, Huang Y, Zhang W, et al. LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer. Journal of Ovarian Research. 2021;14:67. DOI: https://doi.org/10.1186/s13048-021-00807-yGiannopoulou L, Mastoraki S, Buderath P, et al. ESR1 methylation in primary tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer. Gynecologic Oncology. 2018;150(2):355-360. DOI: https://doi.org/10.1016/j.ygyno.2018.05.026Gong G, Lin T, Yuan Y. Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer. Journal of Ovarian Research. 2020;13:30. DOI: https://doi.org/10.1186/s13048-020-00632-9Zhang R, Siu MKY, Ngan HYS, et al. Molecular Biomarkers for the Early Detection of Ovarian Cancer. International Journal of Molecular Sciences. 2022;23(19):12041. DOI: https://doi.org/10.3390/ijms231912041Zagoruiko VA, Nosov AK, Knyazeva MS, et al. Prospects for the application of microRNAs (miR-371, miR-302, miR-372, miR-367) as biomarkers in patients with germ cell tumors. Voprosy onkologii. 2023;69(1):24-29. Russian. DOI: https://doi.org/10.37469/0507-3758-2023-69-1-24-2938. Ho PTB, Clark IM, Le LTT. MicroRNA-based diagnosis and therapy. International Journal of Molecular Sciences. 2022;23(13):7167. DOI: https://doi.org/10.3390/ijms2313716739. Braga EA, Pronina IV, Utkin DO, et al.&nbsp; Hypermethylation of the microRNA miR-124, miR-125b, miR-127, and miR-129 in ovarian carcinoma is involved in suppression of their expression and associated with both the development and progression of ovarian cancer. Almanac of Clinical Medicine. 2019;47(1):47-53. Russian. DOI: https://doi.org/10.18786/2072-0505-2019-47-003Lukina SS, Burdennyy AM, Filippova EA, et al.&nbsp; Clinical features of the microRNA genes methylation in borderline ovarian tumors and depending on the histological structure in ovarian malignancies. Almanac of Clinical Medicine. 2022;50(1):21-30. Russian. DOI: https://doi.org/10.18786/2072-0505-2022-50-001Chen K, Liu MX, Mak CSL, et al. Methylation-associated silencing of miR-193a-3p promotes ovarian cancer aggressiveness by targeting GRB7 and MAPK/ERK pathways. Theranostics. 2018;8(2):423-436. DOI: https://doi.org/10.7150/thno.22377Li T, Li Y, Gan Y, et al. Methylation-mediated repression of MiR-424/503 cluster promotes proliferation and migration of ovarian cancer cells through targeting the hub gene KIF23. Cell Cycle. 2019;18(14):1601-1618. DOI: https://doi.org/10.1080/15384101.2019.1624112