Pathogenic effects of telomerase reverse transcriptase (TERT) promoter mutations in nonalcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) and its potentials as a diagnostic biomarker

Abstract Background Hepatocellular carcinoma (HCC) is the most common type of liver cancer globally due to its diverse aetiologies, poor diagnosis and prognosis as well as low survival rate. Nonalcoholic steatohepatitis-related HCC (NASH-HCC), the progressive form of nonalcoholic fatty liver, is the...

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Main Authors: Usman Umar Liman, Asanka Sudeshini Hawage, Sumadee De Silva, Saumya Madushani Samarasinghe, Kamani Hemamala Tennekoon, Rohan Chaminda Siriwardana, Madunil Anuk Niriella
Format: Article
Language:English
Published: SpringerOpen 2025-06-01
Series:Egyptian Journal of Medical Human Genetics
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Online Access:https://doi.org/10.1186/s43042-025-00738-z
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author Usman Umar Liman
Asanka Sudeshini Hawage
Sumadee De Silva
Saumya Madushani Samarasinghe
Kamani Hemamala Tennekoon
Rohan Chaminda Siriwardana
Madunil Anuk Niriella
author_facet Usman Umar Liman
Asanka Sudeshini Hawage
Sumadee De Silva
Saumya Madushani Samarasinghe
Kamani Hemamala Tennekoon
Rohan Chaminda Siriwardana
Madunil Anuk Niriella
author_sort Usman Umar Liman
collection DOAJ
description Abstract Background Hepatocellular carcinoma (HCC) is the most common type of liver cancer globally due to its diverse aetiologies, poor diagnosis and prognosis as well as low survival rate. Nonalcoholic steatohepatitis-related HCC (NASH-HCC), the progressive form of nonalcoholic fatty liver, is the most prevalent subtype of HCC in this century, and genetic predisposition significantly influences its pathogenesis. Several genes associated with NASH–HCC development have been recently studied. One key regulatory gene is the TERT gene encoding for the TERT protein. Main body of the abstract Hence, the goal of this mini-review is to present the most recent findings about TERT promoter mutations, the mechanism of upregulation of TERT gene expression, the downstream mechanism of promoting NASH-HCC, and its potential as a NASH-HCC diagnostic biomarker. Conclusion Relevant and up-to-date findings were presented in this review, but more thorough researches in multi-ethnic and diver population are needed to determine the prevalence of TERT promoter mutations, its gene expression levels and their potentiality as early diagnostic molecular biomarkers with application in clinical settings. Graphical Abstract
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spelling doaj-art-b8221ee6191c47af8b5a2c1f23ebe77a2025-08-20T03:22:50ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412025-06-0126111710.1186/s43042-025-00738-zPathogenic effects of telomerase reverse transcriptase (TERT) promoter mutations in nonalcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) and its potentials as a diagnostic biomarkerUsman Umar Liman0Asanka Sudeshini Hawage1Sumadee De Silva2Saumya Madushani Samarasinghe3Kamani Hemamala Tennekoon4Rohan Chaminda Siriwardana5Madunil Anuk Niriella6Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Cumarathunga Munidasa MawathaInstitute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Cumarathunga Munidasa MawathaInstitute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Cumarathunga Munidasa MawathaInstitute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Cumarathunga Munidasa MawathaInstitute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Cumarathunga Munidasa MawathaColombo North Center for Liver Diseases, Faculty of Medicine, University of KelaniyaColombo North Center for Liver Diseases, Faculty of Medicine, University of KelaniyaAbstract Background Hepatocellular carcinoma (HCC) is the most common type of liver cancer globally due to its diverse aetiologies, poor diagnosis and prognosis as well as low survival rate. Nonalcoholic steatohepatitis-related HCC (NASH-HCC), the progressive form of nonalcoholic fatty liver, is the most prevalent subtype of HCC in this century, and genetic predisposition significantly influences its pathogenesis. Several genes associated with NASH–HCC development have been recently studied. One key regulatory gene is the TERT gene encoding for the TERT protein. Main body of the abstract Hence, the goal of this mini-review is to present the most recent findings about TERT promoter mutations, the mechanism of upregulation of TERT gene expression, the downstream mechanism of promoting NASH-HCC, and its potential as a NASH-HCC diagnostic biomarker. Conclusion Relevant and up-to-date findings were presented in this review, but more thorough researches in multi-ethnic and diver population are needed to determine the prevalence of TERT promoter mutations, its gene expression levels and their potentiality as early diagnostic molecular biomarkers with application in clinical settings. Graphical Abstracthttps://doi.org/10.1186/s43042-025-00738-zHepatocellular carcinoma (HCC)NAFLDNASH-HCCTelomeresTERT geneTERT promoter mutations
spellingShingle Usman Umar Liman
Asanka Sudeshini Hawage
Sumadee De Silva
Saumya Madushani Samarasinghe
Kamani Hemamala Tennekoon
Rohan Chaminda Siriwardana
Madunil Anuk Niriella
Pathogenic effects of telomerase reverse transcriptase (TERT) promoter mutations in nonalcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) and its potentials as a diagnostic biomarker
Egyptian Journal of Medical Human Genetics
Hepatocellular carcinoma (HCC)
NAFLD
NASH-HCC
Telomeres
TERT gene
TERT promoter mutations
title Pathogenic effects of telomerase reverse transcriptase (TERT) promoter mutations in nonalcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) and its potentials as a diagnostic biomarker
title_full Pathogenic effects of telomerase reverse transcriptase (TERT) promoter mutations in nonalcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) and its potentials as a diagnostic biomarker
title_fullStr Pathogenic effects of telomerase reverse transcriptase (TERT) promoter mutations in nonalcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) and its potentials as a diagnostic biomarker
title_full_unstemmed Pathogenic effects of telomerase reverse transcriptase (TERT) promoter mutations in nonalcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) and its potentials as a diagnostic biomarker
title_short Pathogenic effects of telomerase reverse transcriptase (TERT) promoter mutations in nonalcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) and its potentials as a diagnostic biomarker
title_sort pathogenic effects of telomerase reverse transcriptase tert promoter mutations in nonalcoholic steatohepatitis nash related hepatocellular carcinoma hcc and its potentials as a diagnostic biomarker
topic Hepatocellular carcinoma (HCC)
NAFLD
NASH-HCC
Telomeres
TERT gene
TERT promoter mutations
url https://doi.org/10.1186/s43042-025-00738-z
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