Exome Sequencing Identifies Frequent Inactivating Mutations in BAP1, ARID1A and PBRM1 in Intrahepatic Cholangiocarcinomas

Nat Genet. 2013 Dec;45(12):1470-1473. doi: 10.1038/ng.2813. Epub 2013 Nov 3.

Abstract

Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1, ARID1A and PBRM1), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Duct Neoplasms
  • Bile Ducts, Intrahepatic
  • Cholangiocarcinoma / epidemiology
  • Cholangiocarcinoma / genetics*
  • Cohort Studies
  • Exome / genetics
  • Female
  • Gene Frequency
  • Humans
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / genetics*
  • Male
  • Mutation, Missense*
  • Nuclear Proteins / genetics*
  • Sequence Analysis, DNA
  • Survival Analysis
  • Transcription Factors / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Ubiquitin Thiolesterase / genetics*

Substances

  • ARID1A protein, human
  • BAP1 protein, human
  • Nuclear Proteins
  • PBRM1 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase