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Promoter hypermethylation have been reported to play a key role in bladder cancer development and progression. The aim of this study is to evaluate the methylation status of hTERT, TWIST1, VIM and NID2 genes in bladder cancer. The methylation status was evaluated using the Methylation-Specific PCR (MSP) approach on 70 tumour biopsies from Moroccan bladder cancer patients. Overall, methylation frequencies of hTERT, TWIST1, VIM and NID2 genes, were 90%, 85.71%, 67.14% and 67.14%, respectively. Hypermethylation of all studied genes was found in all pathological grades and stages of bladder cancer. Nevertheless, statistical analysis showed no significant association between promoter methylation of hTERT, TWIST1, VIM and NID2 genes and tumours stage/grade (p value >0.05). Moreover, we have investigated the association between the methylation pattern of selected genes and the treatment outcome in a sub-group of non-muscle-invasive bladder cancer cases (52/70). Hypermethylation of hTERT, TWIST1, VIM and NID2 was detected in 83.34%; 66.67%; 83.34% and 58.34% of recurrent cases, respectively, and in 80%; 80%; 80% and 60% of progressive cases, respectively. Statistical analysis highlighted a significant association between TWIST1 hypermethylation and tumour recurrence (p = 0.041<0.05). Our results indicate that hypermethylation of hTERT, TWIST1, VIM and NID2 genes is a frequent epigenetic event in bladder cancer and could be a promising therapeutic target to prevent bladder cancer progression and metastasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

DNA methylation is the main epigenetic event for gene silencing and is associated with carcinogenesis. In this meta-analysis, we evaluated the association between the methylation of the promoter regions of APC, CADM1, CCNA1, CDH1, DAPK, FHIT, HIC1, MAL, MGMT, hMLH1, P16, PAX1, RAR-β , and RASSF1 genes and the risk of cervical cancer development and progression. Overall, 194 eligible studies were identified assessing the associations of promoter methylation status of aforementioned genes with low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) and cervical cancer development. The majority of studies were conducted on Caucasian and Asian populations, whereas rare studies were available on the African population. Promoter methylation frequencies were shown to be significantly higher in LSIL and HSIL cervical cancer cases as compared to control specimens for CADM1, CCNA1, CDH1, DAPK1, FHIT, MAL, P16, PAX1, RAR-β , and RASSF1 genes. A moderate association was found between HIC promoter methylation, whereas APC, MGMT , and hMLH1 promoter methylation was not correlated with cervical cancer development. Promoter methylation could be considered as a noninvasive biomarker for early cervical lesions, making them highly promising targets for a personalized therapeutic approach., (©2021 American Association for Cancer Research.)

Background: Glutathione S-transferase pi 1 (GSTP1) is a cytosolic detoxifying enzyme that protects cells against deleterious effects of oxidative stress. Deregulated expression of GSTP1 protein and aberrant promoter methylation of GSTP1 gene were reported in various human tumors and were shown to be involved in the molecular pathway for cancer development., Aims and Methods: In this study, we aimed to determine the expression status of GSTP1 in relation to its gene promoter methylation in Moroccan population of 30 bladder cancer (BC) patients and in two noncancerous bladder tissues used as controls. GSTP1 expression was assessed by immunohistochemistry and GSTP1 gene promoter methylation status was studied by methylation-specific PCR (MS-PCR)., Results: Glutathione S-transferase pi 1 was expressed in the two normal tissues. In BC cases, GSTP1 expression was strong in 23.33% (7/30), moderate in 60% (18/30), and weak in 13.33% (4/30) of cases, while GSTP1 was not expressed in one cancer case (3.33%). Variability of GSTP1 expression does not correlate with high-grade cancer or invasive-stage (p > 0.05). No GSTP1 gene promoter methylation was detected in all control and cancer cases., Conclusion: Our data suggest that GSTP1 expression is not associated with BC development, limiting its use as a biomarker for BC management in Morocco. Moreover, difference in GSTP1 expression among BC cases is not due to GSTP1 promoter methylation., (© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Aberrant methylation of tumor suppressor gene promoters has been extensively investigated in cervical cancer. Transcriptional silencing, as a main consequence of hypermethylation of CpG islands, is the predominant mechanism of p16(INK4a) and E-cadherin gene inactivation in malignant epithelial tumors. This study was conducted to evaluate the promoter methylation status of p16(INK4a) and E-cadherin genes in 22 specimens of cervical carcinomas, four cervical cancer cell lines (HeLa, SiHa, Caski, C33A), and 20 human papillomavirus negative specimens, obtained from normal cervical swabs, using the methylation-specific PCR approach. Hypermethylation of the 5' CpG island of the p16(INK4a) and E-cadherin genes were found in 13 (59.1%) and 10 (45.5%) of 22 cervical cancer samples, respectively. Furthermore, our findings did not show any correlation between promoter methylation of p16(INK4a) and E-cadherin genes and clinicopathological parameters, including HPV infection, phenotypic distribution, and stage of the disease. However, hypermethylation of E-cadherin gene promoter appears to be age related in cervical cancer, whereas the frequency of aberrant methylation of p16(INK4a) gene promoter is unchanged according to the age of patients. Thus, caution must be made to use these markers in the diagnosis of cervical cancer. However, dietary or pharmaceutical agents that can inhibit these epigenetic events may prevent or delay the development of cervical cancer.