Common telomerase reverse transcriptase promoter mutations in hepatocellular carcinomas from different geographical locations
World Journal of Gastroenterology
311 - 317
Item Usage Stats
MetadataShow full item record
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.
Telomerase reverse transcriptase
Telomerase reverse transcriptase gene
telomerase reverse transcriptase
hepatocellular carcinoma cell line
liver cell carcinoma
murine double minute 2 gene
polymerase chain reaction
single nucleotide polymorphism
telomerase reverse transcriptase gene
tumor suppressor gene
Published Version (Please cite this version)http://dx.doi.org/10.3748/wjg.v21.i1.311
Showing items related by title, author, creator and subject.
Ozturk, M.; Arslan-Ergul, A.; Bagislar, S.; Senturk, S.; Yuzugullu, H. (Elsevier, 2009-10-01)Cellular senescence is a process leading to terminal growth arrest with characteristic morphological features. This process is mediated by telomere-dependent, oncogene-induced and ROS-induced pathways, but persistent DNA ...
Identification of endogenous reference genes for qRT-PCR analysis in normal matched breast tumor tissues Gur-Dedeoglu, B.; Konu, O.; Bozkurt, B.; Ergul, G.; Seckin, S.; Yulug, I. G. (Cognizant Communication Corporation, 2009)Quantitative gene expression measurements from tumor tissue are frequently compared with matched normal and/or adjacent tumor tissue expression for diagnostic marker gene selection as well as assessment of the degree of ...
Kane, J. K.; Hwang, Y.; Konu, O.; Loughlin, S. E.; Leslie, F. M.; Li, M. D. (Wiley-Blackwell Publishing Ltd., 2005)The present study focuses on the nicotine-induced modulation of mRNA and protein expression of a number of genes involved in glutamatergic synaptic transmission in rat brain over different time periods of exposure. A ...