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

dc.citation.epage317en_US
dc.citation.issueNumber1en_US
dc.citation.spage311en_US
dc.citation.volumeNumber21en_US
dc.contributor.authorCevik, D.en_US
dc.contributor.authorYildiz G.en_US
dc.contributor.authorOzturk, M.en_US
dc.date.accessioned2016-02-08T10:28:21Z
dc.date.available2016-02-08T10:28:21Z
dc.date.issued2015en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractAIM: 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.en_US
dc.identifier.doi10.3748/wjg.v21.i1.311en_US
dc.identifier.issn10079327
dc.identifier.urihttp://hdl.handle.net/11693/24370
dc.language.isoEnglishen_US
dc.publisherWJG Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.3748/wjg.v21.i1.311en_US
dc.source.titleWorld Journal of Gastroenterologyen_US
dc.subjectCellular immortalityen_US
dc.subjectHepatocellular carcinomaen_US
dc.subjectLiver canceren_US
dc.subjectPromoter mutationen_US
dc.subjectTelomerase reverse transcriptaseen_US
dc.subjectTelomerase reverse transcriptase geneen_US
dc.subjectDNA fragmenten_US
dc.subjectgenomic DNAen_US
dc.subjectprotein MDM2en_US
dc.subjecttelomerase reverse transcriptaseen_US
dc.subjectadulten_US
dc.subjectAfricaen_US
dc.subjectAfricanen_US
dc.subjectArticleen_US
dc.subjectAsiaen_US
dc.subjectchromosome 5en_US
dc.subjectclinical articleen_US
dc.subjectcomputer programen_US
dc.subjectcontrolled studyen_US
dc.subjectEuropeen_US
dc.subjectfemaleen_US
dc.subjectgeneen_US
dc.subjectgene amplificationen_US
dc.subjectgene mutationen_US
dc.subjectgene sequenceen_US
dc.subjectgeographic distributionen_US
dc.subjectgeographic originen_US
dc.subjecthepatocellular carcinoma cell lineen_US
dc.subjectheterozygoteen_US
dc.subjecthumanen_US
dc.subjecthuman cellen_US
dc.subjecthuman tissueen_US
dc.subjectliver carcinogenesisen_US
dc.subjectliver cell carcinomaen_US
dc.subjectmaleen_US
dc.subjectmurine double minute 2 geneen_US
dc.subjectmutation rateen_US
dc.subjectmutational analysisen_US
dc.subjectpolymerase chain reactionen_US
dc.subjectprimary tumoren_US
dc.subjectpromoter regionen_US
dc.subjectsingle nucleotide polymorphismen_US
dc.subjecttelomerase reverse transcriptase geneen_US
dc.subjecttumor suppressor geneen_US
dc.subjectwild typeen_US
dc.titleCommon telomerase reverse transcriptase promoter mutations in hepatocellular carcinomas from different geographical locationsen_US
dc.typeArticleen_US
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