TERT promoter mutation in resectable hepatocellular carcinomas: a strong association with hepatitis C infection and absence of hepatitis B infection

Int J Surg. 2014;12(7):659-65. doi: 10.1016/j.ijsu.2014.05.066. Epub 2014 May 24.

Abstract

Introduction: Mutation in the core promoter of the telomerase reverse transcriptase (TERT) gene was determined to be a frequent event in malignant melanoma and other cancers. However, the role of TERT promoter mutation in hepatocellular carcinomas (HCCs) remains largely unknown.

Methods: Genomic DNA samples from the tumor tissue of 195 HCCs were analyzed for TERT promoter mutation at 2 hotspots (-124 and -146 bp from the ATG start site, g.1,295,228 and g.1,295,250, respectively) through direct sequencing.

Results: The TERT promoter mutation was identified in 57 of the 195 HCCs (29.2%) and was associated with old age (P = 0.0122), presence of anti-hepatitis C (HCV; P = 0.0048), and absence of hepatitis B surface antigen (HBsAg; P = 0.0007). However, the TERT promoter mutation did not correlate with serum α-fetoprotein levels, liver cirrhosis, tumor size, tumor grade, tumor stage, early tumor recurrence, β-catenin mutation or p53 mutation. A multivariate analysis confirmed that the absence of hepatitis B infection is an independent factor associated with TERT promoter mutation. Furthermore, among HCC patients infected with hepatitis C, those with concomitant hepatitis B infection exhibited infrequent TERT promoter mutation (P = 0.0435). Remarkably, patients presenting with TERT promoter mutation-positive and -negative HCCs exhibited similar disease-free and overall survival rates.

Conclusions: Our study indicated that the TERT promoter mutation frequently occurred in HCV-associated HCCs. The absence of Hepatitis B infection was significantly associated with the TERT promoter mutation. These findings suggest that various etiological factors may be involved in differing mechanisms to preserve telomeres during the carcinogenesis of HCCs.

Keywords: HCC; Hepatitis B; Hepatitis C; Promoter mutation; TERT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Cohort Studies
  • Female
  • Hepatitis B / complications
  • Hepatitis C / complications*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Mutation
  • Promoter Regions, Genetic*
  • Risk Factors
  • Survival Analysis
  • Telomerase / genetics*

Substances

  • TERT protein, human
  • Telomerase