The PTENP1 Pseudogene, Unlike the PTEN Gene, Is Methylated in Normal Endometrium, As Well As in Endometrial Hyperplasias and Carcinomas in Middle-Aged and Elderly Females.

The tumor suppressor PTEN controls multiple cellular functions, including cell cycle, apoptosis, senescence, transcription, and mRNA translation of numerous genes. In tumor cells, PTEN is frequently inactivated by genetic mutations and epimutations. The aim of this study was to investigate the methylation patterns of the gene and its pseudogene as potential genetic markers of endometrial hyperplasia (EH) and endometrial carcinoma (EC). Methylation of the 5'-terminal regions of the and sequences was studied using methyl-sensitive PCR of genomic DNA isolated from 57 cancer, 43 endometrial hyperplasia, and normal tissue samples of 24 females aged 17-34 years and 19 females aged 45-65 years, as well as 20 peripheral venous blood samples of EC patients. None of the analyzed DNA samples carried a methylated gene. On the contrary, the pseudogene was methylated in all analyzed tissues, except for the peripheral blood. Comparison of methylation rates revealed no differences between the EC and EH groups (0.80 < < 0.50). In all these groups, the methylation level was high (71-77% in patients . 58% in controls). Differences in methylation rates between normal endometrium in young (4%) and middle-aged and elderly (58%) females were significant ( < 0.001). These findings suggest that pseudogene methylation may reflect age-related changes in the body and is not directly related to the endometrium pathology under study. It is assumed that, depending on the influence of a methylated pseudogene on gene expression, the pseudogene methylation may protect against the development of EC and/or serve as a marker of a precancerous condition of endometrial cells.