title: TERT promoter mutation in resectable hepatocellular carcinomas: a strong association with hepatitis C infection and absence of hepatitis B infection.
abstract: BACKGROUND
  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.
authors.affiliation: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pathology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.affiliation: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chih-Ning
authors.initials: CN
authors.lastname: Chang
authors.affiliation: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsin-Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hey-Chi
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Department of Pathology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Lai
authors.affiliation: Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10051, Taiwan. Electronic address: d83409009@ntu.edu.tw.
authors.forename: Ray-Hwang
authors.initials: RH
authors.lastname: Yuan
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D015331:Cohort Studies; D005260:Female; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D016019:Survival Analysis; D019098:Telomerase / Q000235:genetics*
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: HCC; Hepatitis B; Hepatitis C; Promoter mutation; TERT