High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions

Nat Commun. 2013;4:2218. doi: 10.1038/ncomms3218.

Abstract

Somatic mutations activating telomerase reverse-trancriptase promoter were recently identified in several tumour types. Here we identify frequent similar mutations in human hepatocellular carcinomas (59%), cirrhotic preneoplastic macronodules (25%) and hepatocellular adenomas with malignant transformation in hepatocellular carcinomas (44%). In hepatocellular tumours, telomerase reverse-transcripase- and CTNNB1-activating mutations are significantly associated. Moreover, preliminary data suggest that telomerase reverse-trancriptase promoter mutations can increase the expression of telomerase transcript. In conclusion, telomerase reverse-trancriptase promoter mutation is the earliest recurrent genetic event identified in cirrhotic preneoplastic lesions so far and is also the most frequent genetic alteration in hepatocellular carcinomas, arising from both the cirrhotic or non-cirrhotic liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Liver Cell / genetics*
  • Adenoma, Liver Cell / metabolism
  • Adenoma, Liver Cell / pathology
  • Aged
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Gene Expression
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Telomerase / genetics*
  • Telomerase / metabolism
  • beta Catenin / genetics*
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • RNA, Messenger
  • beta Catenin
  • TERT protein, human
  • Telomerase