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

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, ß-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.