Promoter hypermethylation of TERT is associated with hepatocellular carcinoma in the Han Chinese population

Abstract

Background: Upstream of the transcription start site (UTSS), hypermethylation of the telomerase reverse transcriptase (TERT) gene has been shown to be associated with tumour progression and a poor prognosis in paediatric brain tumours (Castelo-Branco 2013). It has been inferred that the UTSS region of TERT is a potentially accessible biomarker for various cancers. In this study, we aimed to explore the role of TERT in hepatocellular carcinoma (HCC) and to investigate whether the UTSS region of the TERT promoter shows the same methylation pattern in HCC.

Methods: We analysed the results of a methylation assay for TERT, including the UTSS region, from 125 paired HCC samples using Mass Array EpiTyper (Sequenom, San Diego, CA, USA). To determine the relationship between TERT promoter methylation status and the TERT expression level, we analysed a validation group of 12 paired HCC samples and acquired the FPKM values for the TERT gene.

Results: Our results showed aberrant methylation of the UTSS region of the TERT promoter in HCC (mean=15.1) compared with the adjacent normal tissues (mean=6.1, P<0.00001). Furthermore, a nearly 56-fold increase in TERT expression from the hypermethylated promoter was found in HCC (P<0.05), indicating a positive relationship between TERT methylation and expression.

Conclusions: As hypermethylation was positively correlated with high expression of TERT in HCC, TERT is likely to be involved in the aetiology of HCC. Our findings indicate that future studies on TERT might be fruitful.