TERT promoter mutation in resectable hepatocellular carcinomas: A strong association with hepatitis C infection and absence of hepatitis B infection
Journal
International Journal of Surgery
Journal Volume
12
Journal Issue
7
Pages
659-665
Date Issued
2014
Author(s)
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. ? 2014 Surgical Associates Ltd.
SDGs
Other Subjects
alpha fetoprotein; beta catenin; genomic DNA; hepatitis B surface antigen; hepatitis C antibody; messenger RNA; protein p53; telomerase reverse transcriptase; telomerase; TERT protein, human; genomic DNA; thymocyte antibody; adolescent; adult; age; aged; alpha fetoprotein blood level; article; cancer grading; cancer recurrence; cancer size; cancer staging; child; clinical feature; cohort analysis; disease association; disease free survival; DNA determination; DNA sequence; female; follow up; gene expression; gene mutation; genetic variability; hepatitis B; hepatitis C; histopathology; human; human tissue; liver cell carcinoma; liver cirrhosis; liver parenchyma; major clinical study; male; overall survival; priority journal; promoter region; real time polymerase chain reaction; survival rate; complication; genetics; hepatitis B; hepatitis C; liver cell carcinoma; liver tumor; middle aged; mutation; risk factor; survival; virology; Article; cancer surgery; cancer survival; cancer tissue; carcinogenesis; clinical assessment; comparative study; correlational study; gene frequency; gene sequence; genetic identification; liver cell carcinoma; mutation rate; promoter region; senescence; tumor recurrence; tumor volume; Carcinoma, Hepatocellular; Cohort Studies; Female; Hepatitis B; Hepatitis C; Humans; Liver Neoplasms; Male; Middle Aged; Mutation; Promoter Regions, Genetic; Risk Factors; Survival Analysis; Telomerase
Publisher
Elsevier Ltd
Type
journal article