Common telomerase reverse transcriptase promoter mutations in hepatocellular carcinomas from different geographical locations

Cevik, D.
Yildiz G.
Ozturk, M.
Source Title
World Journal of Gastroenterology
Print ISSN
Electronic ISSN
WJG Press
311 - 317
Journal Title
Journal ISSN
Volume Title

AIM: To determine the mutation status of human telomerase reverse transcriptase gene (TERT ) promoter region in hepatocellular carcinoma (HCC) from different geographical regions. METHODS: We analyzed the genomic DNA sequences of 59 HCC samples comprising 15 cell lines and 44 primary tumors, collected from patients living in Asia, Europe and Africa. We amplified a 474 bp DNA fragment of the promoter region of TERT gene including the 1295228 and 1295250 sequence of chromosome 5 by using PCR. Amplicons were then sequenced by Sanger technique and the sequence data were analyzed with by using DNADynamo software in comparison with wild type TERT gene sequence as a reference. RESULTS: The TERT mutations were found highly frequent in HCC. Eight of the fifteen tested cell lines displayed C228T mutation, and one had C250T mutation with a mutation frequency up to 60%. All of the mutations were heterozygous and mutually exclusive. Ten out of forty-four tumors displayed C228T mutation, and additional five tumors had C250T mutation providing evidence for mutation frequency of 34% in primary tumors. Considering the geographic origins of HCC tumors tested, TERT promoter mutation frequencies were higher in African (53%), when compared to non-African (24%) tumors (P = 0.056). There was also a weak inverse correlation between TERT promoter mutations and murine double minute 2 single nucleotide polymorphism 309 TG polymorphism (P = 0.058). Mutation frequency was nearly two times higher in established HCC cell lines (60%) compared to the primary tumors (34%). CONCLUSION: TERT promoter is one of most frequent mutational targets in liver cancer, and hepatocellular carcinogenesis is highly associated with the loss of telomere-dependent cellular senescence control. © The Author(s) 2015.

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Book Title
Cellular immortality, Hepatocellular carcinoma, Liver cancer, Promoter mutation, Telomerase reverse transcriptase, Telomerase reverse transcriptase gene, DNA fragment, genomic DNA, protein MDM2, telomerase reverse transcriptase, adult, Africa, African, Article, Asia, chromosome 5, clinical article, computer program, controlled study, Europe, female, gene, gene amplification, gene mutation, gene sequence, geographic distribution, geographic origin, hepatocellular carcinoma cell line, heterozygote, human, human cell, human tissue, liver carcinogenesis, liver cell carcinoma, male, murine double minute 2 gene, mutation rate, mutational analysis, polymerase chain reaction, primary tumor, promoter region, single nucleotide polymorphism, telomerase reverse transcriptase gene, tumor suppressor gene, wild type
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