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The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma

Telomerase activation via induction of the catalytic component telomerase reverse transcriptase (TERT) plays essential roles in malignant transformation. TERT promoter-activating mutations were recently identified as a novel mechanism to activate telomerase in hepatocellular carcinoma (HCC) and many...

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Autores principales: Yuan, Xiaotian, Cheng, Guanghui, Yu, Jingya, Zheng, Shunzhen, Sun, Chao, Sun, Qing, Li, Kailin, Lin, Zhaomin, Liu, Tiantian, Li, Ping, Xu, Yiteng, Kong, Feng, Bjorkholm, Magnus, Xu, Dawei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410290/
https://www.ncbi.nlm.nih.gov/pubmed/28416747
http://dx.doi.org/10.18632/oncotarget.15498
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author Yuan, Xiaotian
Cheng, Guanghui
Yu, Jingya
Zheng, Shunzhen
Sun, Chao
Sun, Qing
Li, Kailin
Lin, Zhaomin
Liu, Tiantian
Li, Ping
Xu, Yiteng
Kong, Feng
Bjorkholm, Magnus
Xu, Dawei
author_facet Yuan, Xiaotian
Cheng, Guanghui
Yu, Jingya
Zheng, Shunzhen
Sun, Chao
Sun, Qing
Li, Kailin
Lin, Zhaomin
Liu, Tiantian
Li, Ping
Xu, Yiteng
Kong, Feng
Bjorkholm, Magnus
Xu, Dawei
author_sort Yuan, Xiaotian
collection PubMed
description Telomerase activation via induction of the catalytic component telomerase reverse transcriptase (TERT) plays essential roles in malignant transformation. TERT promoter-activating mutations were recently identified as a novel mechanism to activate telomerase in hepatocellular carcinoma (HCC) and many other malignancies. In addition, single nucleotide polymorphisms (SNPs) in the TERT rs2736098 and rs2736100 are significantly associated with cancer susceptibility. It is currently unclear whether different germline TERT variants modify TERT promoter mutations. Here we analyzed the TERT promoter status and genotyped the TERT SNPs at rs2736098 and rs2736100 in patients with HCC. Thirty percent of HCCs harbored TERT promoter mutations and there was a significant difference in rs2736098 and rs2736100 genotypes between wt and mutant TERT promoter-bearing HCC tumors (P = 0.007 and 0.018, respectively). For rs2736100, the cancer risk genotype CC was significantly associated with a reduced incidence of TERT promoter mutations compared to AA + AC variants [Odds ratio (OR): 0.181, 95% Confidence interval (CI): 0.0543–0.601, P = 0.004]. The rs2736098_CT genotype was significantly associated with the TERT promoter mutation-positive tumors compared to the TT genotype (OR: 5.391, 95% CI: 1.234–23.553, P = 0.025). These differences in genotype distribution did not differ between patients with a wt TERT promoter and controls. The presence of TERT promoter mutations was not associated with clinico-pathological variables. Taken together, the germline TERT genetic background may significantly affect the onset of TERT promoter mutations in HCCs, which provides a better understanding of HCC-related TERT promoter mutations and telomerase regulation in cancer.
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spelling pubmed-54102902017-05-04 The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma Yuan, Xiaotian Cheng, Guanghui Yu, Jingya Zheng, Shunzhen Sun, Chao Sun, Qing Li, Kailin Lin, Zhaomin Liu, Tiantian Li, Ping Xu, Yiteng Kong, Feng Bjorkholm, Magnus Xu, Dawei Oncotarget Research Paper Telomerase activation via induction of the catalytic component telomerase reverse transcriptase (TERT) plays essential roles in malignant transformation. TERT promoter-activating mutations were recently identified as a novel mechanism to activate telomerase in hepatocellular carcinoma (HCC) and many other malignancies. In addition, single nucleotide polymorphisms (SNPs) in the TERT rs2736098 and rs2736100 are significantly associated with cancer susceptibility. It is currently unclear whether different germline TERT variants modify TERT promoter mutations. Here we analyzed the TERT promoter status and genotyped the TERT SNPs at rs2736098 and rs2736100 in patients with HCC. Thirty percent of HCCs harbored TERT promoter mutations and there was a significant difference in rs2736098 and rs2736100 genotypes between wt and mutant TERT promoter-bearing HCC tumors (P = 0.007 and 0.018, respectively). For rs2736100, the cancer risk genotype CC was significantly associated with a reduced incidence of TERT promoter mutations compared to AA + AC variants [Odds ratio (OR): 0.181, 95% Confidence interval (CI): 0.0543–0.601, P = 0.004]. The rs2736098_CT genotype was significantly associated with the TERT promoter mutation-positive tumors compared to the TT genotype (OR: 5.391, 95% CI: 1.234–23.553, P = 0.025). These differences in genotype distribution did not differ between patients with a wt TERT promoter and controls. The presence of TERT promoter mutations was not associated with clinico-pathological variables. Taken together, the germline TERT genetic background may significantly affect the onset of TERT promoter mutations in HCCs, which provides a better understanding of HCC-related TERT promoter mutations and telomerase regulation in cancer. Impact Journals LLC 2017-02-18 /pmc/articles/PMC5410290/ /pubmed/28416747 http://dx.doi.org/10.18632/oncotarget.15498 Text en Copyright: © 2017 Yuan et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Yuan, Xiaotian
Cheng, Guanghui
Yu, Jingya
Zheng, Shunzhen
Sun, Chao
Sun, Qing
Li, Kailin
Lin, Zhaomin
Liu, Tiantian
Li, Ping
Xu, Yiteng
Kong, Feng
Bjorkholm, Magnus
Xu, Dawei
The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma
title The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma
title_full The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma
title_fullStr The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma
title_full_unstemmed The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma
title_short The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma
title_sort tert promoter mutation incidence is modified by germline tert rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410290/
https://www.ncbi.nlm.nih.gov/pubmed/28416747
http://dx.doi.org/10.18632/oncotarget.15498
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