Studies on the Role of hTERT – a Telomerase Regulator of DNA Methylation in Cervical Cancer

Abstract

Telomerase is a cellular reverse transcriptase which stabilizes telomere length by adding hexameric TTAGGG repeats onto the telomeric ends of chromosomes. Expression of telomerase occurs in germ cells and stem cells but not in normal (somatic) cells. However, in many tumors, telomerase is activated, which is one of the immortalization steps. In humans, telomerase expression is regulated by a telomerase subunit called hTERT. The promoter region of the gene that encodes hTERT is located in a CpG island and was shown to be regulated, at least in part, by DNA methylation. In this study, we have analyzed the methylation status of the hTERT gene in primary squamous cell carcinomas, SCC-1 and SCC-2, and HPV+ cervical tissue scrapes, moderate dyskaryosis and mild dyskaryosis. By using the bisulfite genomic sequencing assay, the region between +90 bp and +566 bp within the gene was analyzed. We found that the primary squamous cell carcinoma SCC-1, which consists of 70% carcinoma cells, was more methylated than SCC-2, which consisted of 40% carcinoma cells. However, the number of methylated CpGs in cervical scrapes classified as moderate dyskaryosis and mild dyskaryosis were higher than in SCC-2. In the present study, we demonstrated the importance of DNA methylation profile at hTERT promoter site as a promising biomarker for cervical cancer. Further, it also provides a possible mechanism into the epigenetic regulation of hTERT in various other cancer developments.