Hong Zhang1, Xiaoling Weng1, Junyi Ye1, Lin He2, Daizhan Zhou3, Yun Liu4. 1. Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China. 2. Bio-X Centre Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, PR China. 3. 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. 4. Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China. Electronic address: superliuyun@gmail.com.
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.
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: Donghyun D Lee; Ricardo Leão; Martin Komosa; Marco Gallo; Cindy H Zhang; Tatiana Lipman; Marc Remke; Abolfazl Heidari; Nuno Miguel Nunes; Joana D Apolónio; Aryeh J Price; Ramon Andrade De Mello; João S Dias; David Huntsman; Thomas Hermanns; Peter J Wild; Robert Vanner; Gelareh Zadeh; Jason Karamchandani; Sunit Das; Michael D Taylor; Cynthia E Hawkins; Jonathan D Wasserman; Arnaldo Figueiredo; Robert J Hamilton; Mark D Minden; Khalida Wani; Bill Diplas; Hai Yan; Kenneth Aldape; Mohammad R Akbari; Arnavaz Danesh; Trevor J Pugh; Peter B Dirks; Pedro Castelo-Branco; Uri Tabori Journal: J Clin Invest Date: 2018-12-03 Impact factor: 14.808
Authors: Donghyun D Lee; Martin Komosa; Sumedha Sudhaman; Ricardo Leão; Cindy H Zhang; Joana D Apolonio; Thomas Hermanns; Peter J Wild; Helmut Klocker; Farshad Nassiri; Gelareh Zadeh; Bill H Diplas; Hai Yan; Steven Gallinger; Trevor J Pugh; Vijay Ramaswamy; Michael D Taylor; Pedro Castelo-Branco; Nuno Miguel Nunes; Uri Tabori Journal: J Clin Invest Date: 2021-11-01 Impact factor: 14.808
Authors: Érica S S de Araújo; Dimitrius T Pramio; André Y Kashiwabara; Paula C Pennacchi; Silvya S Maria-Engler; Maria I Achatz; Antonio H J F M Campos; João P Duprat; Carla Rosenberg; Dirce M Carraro; Ana C V Krepischi Journal: Biomed Res Int Date: 2015-04-12 Impact factor: 3.411
Authors: Maria M Simile; Gavinella Latte; Maria I Demartis; Stefania Brozzetti; Diego F Calvisi; Alberto Porcu; Claudio F Feo; Maria A Seddaiu; Lucia Daino; Carmen Berasain; Maria L Tomasi; Matias A Avila; Francesco Feo; Rosa M Pascale Journal: Oncotarget Date: 2016-08-02