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, Guhung Jung

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)684-699
Number of pages16
JournalOncotarget
Volume7
Issue number1
DOIs
Publication statusPublished - 2016 Jan 5

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Keywords

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

ASJC Scopus subject areas

  • Oncology

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