IMPLICATIONS AND POTENTIAL ROLE OF HUMAN TELOMERASE REVERSE TRANSCRIPTASE (HTERT) IN BLADDER CARCINOGENESIS

Bladder cancer is a heterogeneous disease and ranks as 10th most common cancer worldwide. Urothelial carcinoma (UC) is the most common histologic type of BC and majority constitute of papillary tumors that are well-differentiated (low-grade). Several genetic changes may occur in bladder cancer, but hTERT promoter mutations and its expression has been detected in most cases of transitional cell carcinoma. Numerous researches have led to the findings which suggest that the hTERT promoter mutations in conjunction with the common polymorphism and hTERT expression have potential of being used as clinical biomarkers in bladder cancer. Further studies need to explore the potential use of hTERT gene in bladder cancer detection, diagnosis and prognosis. This review focuses on the role of hTERT in bladder tumors in the backdrop of various studies published.

Efficacy of decitabine in malignant meningioma cells: relation to promoter demethylation of distinct tumor suppressor and oncogenes and independence from TERT

OBJECTIVEChemotherapeutic options for meningiomas refractory to surgery or irradiation are largely unknown. Human telomerase reverse transcriptase (hTERT) promoter methylation with subsequent TERT expression and telomerase activity, key features in oncogenesis, are found in most high-grade meningiomas. Therefore, the authors investigated the impact of the demethylating agent decitabine (5-aza-2ʹ-deoxycytidine) on survival and DNA methylation in meningioma cells.METHODShTERT promoter methylation, telomerase activity, TERT expression, and cell viability and proliferation were investigated prior to and after incubation with decitabine in two benign (HBL-52 and Ben-Men 1) and one malignant (IOMM-Lee) meningioma cell line. The global effects of decitabine on DNA methylation were additionally explored with DNA methylation profiling.RESULTSHigh levels of TERT expression, telomerase activity, and hTERT promoter methylation were found in IOMM-Lee and Ben-Men 1 but not in HBL-52 cells. Decitabine induced a dose-dependent significant decrease of proliferation and viability after incubation with doses from 1 to 10 μM in IOMM-Lee but not in HBL-52 or Ben-Men 1 cells. However, effects in IOMM-Lee cells were not related to TERT expression, telomerase activity, or hTERT promoter methylation. Genome-wide methylation analyses revealed distinct demethylation of 14 DNA regions after drug administration in the decitabine-sensitive IOMM-Lee but not in the decitabine-resistant HBL-52 cells. Differentially methylated regions covered promoter regions of 11 genes, including several oncogenes and tumor suppressor genes that to the authors’ knowledge have not yet been described in meningiomas.CONCLUSIONSDecitabine decreases proliferation and viability in high-grade but not in benign meningioma cell lines. The effects of decitabine are TERT independent but related to DNA methylation changes of promoters of distinct tumor suppressor genes and oncogenes.