Common telomerase reverse transcriptase promoter mutations in hepatocellular carcinomas from different geographical locations
dc.citation.epage | 317 | en_US |
dc.citation.issueNumber | 1 | en_US |
dc.citation.spage | 311 | en_US |
dc.citation.volumeNumber | 21 | en_US |
dc.contributor.author | Cevik, D. | en_US |
dc.contributor.author | Yildiz G. | en_US |
dc.contributor.author | Ozturk, M. | en_US |
dc.date.accessioned | 2016-02-08T10:28:21Z | |
dc.date.available | 2016-02-08T10:28:21Z | |
dc.date.issued | 2015 | en_US |
dc.department | Department of Molecular Biology and Genetics | en_US |
dc.description.abstract | 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. | en_US |
dc.description.provenance | Made available in DSpace on 2016-02-08T10:28:21Z (GMT). No. of bitstreams: 1 bilkent-research-paper.pdf: 70227 bytes, checksum: 26e812c6f5156f83f0e77b261a471b5a (MD5) Previous issue date: 2015 | en |
dc.identifier.doi | 10.3748/wjg.v21.i1.311 | en_US |
dc.identifier.issn | 10079327 | |
dc.identifier.uri | http://hdl.handle.net/11693/24370 | |
dc.language.iso | English | en_US |
dc.publisher | WJG Press | en_US |
dc.relation.isversionof | http://dx.doi.org/10.3748/wjg.v21.i1.311 | en_US |
dc.source.title | World Journal of Gastroenterology | en_US |
dc.subject | Cellular immortality | en_US |
dc.subject | Hepatocellular carcinoma | en_US |
dc.subject | Liver cancer | en_US |
dc.subject | Promoter mutation | en_US |
dc.subject | Telomerase reverse transcriptase | en_US |
dc.subject | Telomerase reverse transcriptase gene | en_US |
dc.subject | DNA fragment | en_US |
dc.subject | genomic DNA | en_US |
dc.subject | protein MDM2 | en_US |
dc.subject | telomerase reverse transcriptase | en_US |
dc.subject | adult | en_US |
dc.subject | Africa | en_US |
dc.subject | African | en_US |
dc.subject | Article | en_US |
dc.subject | Asia | en_US |
dc.subject | chromosome 5 | en_US |
dc.subject | clinical article | en_US |
dc.subject | computer program | en_US |
dc.subject | controlled study | en_US |
dc.subject | Europe | en_US |
dc.subject | female | en_US |
dc.subject | gene | en_US |
dc.subject | gene amplification | en_US |
dc.subject | gene mutation | en_US |
dc.subject | gene sequence | en_US |
dc.subject | geographic distribution | en_US |
dc.subject | geographic origin | en_US |
dc.subject | hepatocellular carcinoma cell line | en_US |
dc.subject | heterozygote | en_US |
dc.subject | human | en_US |
dc.subject | human cell | en_US |
dc.subject | human tissue | en_US |
dc.subject | liver carcinogenesis | en_US |
dc.subject | liver cell carcinoma | en_US |
dc.subject | male | en_US |
dc.subject | murine double minute 2 gene | en_US |
dc.subject | mutation rate | en_US |
dc.subject | mutational analysis | en_US |
dc.subject | polymerase chain reaction | en_US |
dc.subject | primary tumor | en_US |
dc.subject | promoter region | en_US |
dc.subject | single nucleotide polymorphism | en_US |
dc.subject | telomerase reverse transcriptase gene | en_US |
dc.subject | tumor suppressor gene | en_US |
dc.subject | wild type | en_US |
dc.title | Common telomerase reverse transcriptase promoter mutations in hepatocellular carcinomas from different geographical locations | en_US |
dc.type | Article | en_US |
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