title: 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.
authors: Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China.
authors: Hong
authors: H
authors: Zhang
authors: Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China.
authors: Xiaoling
authors: X
authors: Weng
authors: Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China.
authors: Junyi
authors: J
authors: Ye
authors: Bio-X Centre Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, PR China.
authors: Lin
authors: L
authors: He
authors: Bio-X Centre Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, PR China. Electronic address: zhoudaizhan@gmail.com.
authors: Daizhan
authors: D
authors: Zhou
authors: Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China. Electronic address: superliuyun@gmail.com.
authors: Yun
authors: Y
authors: Liu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D002681:China; D019175:DNA Methylation / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C509186:TERT protein, human; D019098:Telomerase