DNA methylation and the activity pattern of DNA methyltransferase (DNMT1) in endometrial carcinoma

Introduction: Endometrial cancer is the sixth most common malignancy among the female population worldwide, and the most frequently recognized tumor of the female genital tract. DNA methylation plays an important role in the epigenetic regulation of gene expression during cell development and disease status. The complex of events in the DNA methylation pattern greatly depends on the catalytic role of DNA-specific enzymes called methyltransferases. Objectives: The aim of our study was to compare DNA methylation and DNMT1 activity pattern in endometrial cancer tissues collected from three distinct areas of the uterine cavity, and to evaluate the prognostic value of the enzymatic role of DNMT1. Material and methods: The study group consisted of 37 women (28 with the diagnosis of endometrial adenocarcinoma and 9 with uterine fibroids) who underwent hysterectomy at the II Department of Gynecology, Medical University of Lublin, between 2008 and 2009. Tissue specimens were obtained for the purpose of the study from three distinct uterine sites (84 cancerous tissue specimens and 27 healthy endometrium samples in total). A standardized protocol with the use of commercial kits (Epigentek, USA) was used for all of the collected samples. U Mann Whitney and W Shapiro-Wilk tests were used to compare the results. Results: DNA methylation levels as well as DNMT1 activity levels were significantly lower (3.83 vs. 7.65 OD/h/mg; p=0.0022) in the endometrial adenocarcinoma tissues collected from the uterine cavity as compared to healthy endometrial tissues. Conclusions: Global DNA hypomethylation and significantly lower DNMT1 activity observed in the endometrial adenocarcinoma samples in comparison to healthy endometrial tissue can be putative molecular markers of carcinogenesis. Further studies are needed to confirm this hypothesis.