Research Papers:

The TERT promoter SNP rs2853669 decreases E2F1 transcription factor binding and increases mortality and recurrence risks in liver cancer

Eunkyong Ko, Hyun-Wook Seo, Eun Sun Jung, Baek-hui Kim and Guhung Jung _

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Oncotarget. 2016; 7:684-699. https://doi.org/10.18632/oncotarget.6331

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Eunkyong Ko1, Hyun-Wook Seo1, Eun Sun Jung2, Baek-hui Kim3, Guhung Jung1

1Department of Biological Sciences, College of Natural Sciences, Seoul National University, Gwanak-gu, Seoul, 151-747, South Korea

2Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seocho-Gu, Seoul, 133-782, South Korea

3Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, 152-703, South Korea

Correspondence to:

Guhung Jung, e-mail: [email protected]

Keywords: single-nucleotide polymorphism at telomerase reverse transcriptase (TERT) promoter, TERT promoter mutation, risk of hepatocellular carcinoma (HCC)-related mortality and recurrence, mechanism for regulation of SNP-dependent TERT promoter activity, A TERT transcription repressor

Received: August 21, 2015     Accepted: October 27, 2015     Published: November 09, 2015


A common single-nucleotide polymorphism in the telomerase reverse transcriptase (TERT) promoter, rs2853669 influences patient survival rates and the risk of developing cancer. Recently, several lines of evidence suggest that the rs2853669 suppresses TERT promoter mutation-mediated TERT expression levels and cancer mortality as well as recurrence rates. However, no reports are available on the impact of rs2853669 on TERT expression in hepatocellular carcinoma (HCC) and its association with patient survival. Here, we found that HCC-related overall and recurrence-free survival rates were not associated with TERT promoter mutation individually, but rs2853669 and the TERT promoter mutation in combination were associated with poor survival rates. TERT mRNA expression and telomere fluorescence levels were greater in patients with HCC who had both the combination. The combination caused TERT promoter methylation through regulating the binding of DNA methyltransferase 1 and histone deacetylase 1 to the TERT promoter in HCC cell lines. The TERT expression level was significantly higher in HCC tumor with a methylated promoter than in that with an unmethylated promoter. In conclusion, we demonstrate a substantial role for the rs2853669 in HCC with TERT promoter mutation, which suggests that the combination of the rs2853669 and the mutation indicate poor prognoses in liver cancer.

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