Mutational landscape of intrahepatic cholangiocarcinoma

Nat Commun. 2014 Dec 15;5:5696. doi: 10.1038/ncomms6696.


Intrahepatic cholangiocarcinoma (ICC) is a fatal primary liver cancer (PLC) that affects 5-10% of all PLCs. Here we sequence tumour and matching control sample pairs of a large cohort of 103 ICC patients in China, resulting in the identification of an ICC-specific somatic mutational signature that is associated with liver inflammation, fibrosis and cirrhosis. We further uncover 25 significantly mutated genes including eight potential driver genes (TP53, KRAS, IDH1, PTEN, ARID1A, EPPK1, ECE2 and FYN). We find that TP53-defective ICC patients are more likely to be HBsAg-seropositive, whereas mutations in the oncogene KRAS are nearly exclusively found in HBsAg-seronegative ICC patients. Three pathways (Ras/phosphatidylinositol-4,5-bisphosphate 3-kinase signalling, p53/cell cycle signalling and transforming growth factor-β/Smad signalling), genes important for epigenetic regulation and oxidative phosphorylation are substantially affected in ICC. We reveal mutations in this study that may be valuable for designing further studies, better diagnosis and effective therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bile Duct Neoplasms / genetics*
  • Bile Ducts, Intrahepatic
  • China
  • Cholangiocarcinoma / genetics*
  • Cohort Studies
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Liver Neoplasms / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • PTEN Phosphohydrolase / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Tumor Suppressor Protein p53 / genetics
  • ras Proteins / genetics


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins

Associated data

  • SRA/SRP045202