Cholangiocarcinoma (CHOL)

Overview

Cholangiocarcinoma (CCA) is a malignancy arising from the biliary epithelium. In OncoTree, CHOL is the umbrella code encompassing both intrahepatic cholangiocarcinoma (IHCH) and extrahepatic cholangiocarcinoma (EHCH), which includes perihilar (Klatskin) and distal subtypes. CCA has overlapping histology and biology with hepatocellular carcinoma (HCC), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a recognised mixed entity.

Cohorts in the corpus

  • No dedicated CHOL-coded datasets in the corpus; see IHCH and EHCH for subtype-specific cohort links.

Recurrent alterations

  • Narrative review of etiology-driven genomic landscape across CCA subtypes: iCCA enriched for IDH1 (13-29%), FGFR2 fusions (8-16%), ARID1A (18-23%), KRAS (24-27%), TP53 (20-27%); eCCA enriched for KRAS (37-46%), TP53 (35-68%), SMAD4 (~25%); HBV integration near TERT and MET; HCV association with FGFR2 fusions (OR 9.50); PSC-CCA enriched for TP53/KRAS/SMAD4/ERBB2; CDKN2A/B (15-27% iCCA, 19% eCCA) mediates acquired FGFR-inhibitor resistance PMID:25526346.
  • Narrative review of gut-liver axis dysregulation in cholangiocarcinoma identifies gut microbiota dysbiosis, bile acid metabolic reprogramming (conjugated primary BAs accumulate; a CDCA+TCDCA panel outperformed CA19-9, AUC=0.95), and LPS/TLR4-driven immunosuppression as CCA progression mechanisms; ivosidenib (IDH1-mutant iCCA) and futibatinib (FGFR2-rearranged iCCA) are highlighted as precision therapeutics. PMID:25608663
  • ICGC multi-omic profiling of 489 cholangiocarcinomas from 10 countries defined four etiology-driven molecular clusters, nominating ERBB2 amplification (10.4% Fluke-Pos), IDH1/IDH2 mutations, FGFR2 rearrangements, and four new drivers (RASA1, STK11, MAP2K4, SF3B1); integrative clusters predicted prognosis independently of anatomical location and fluke status. PMID:28667006
  • Biliary tract cancer (cholangiocarcinoma) showed responses to neratinib in the SUMMIT basket trial for HER2/HER3-mutant solid tumors, including HER2 kinase domain missense mutations (L755, V777), contributing to the lineage-plus-allele pattern of pan-HER TKI sensitivity PMID:29420467
  • Pan-cancer fusion study (9,624 TCGA samples) identified FGFR2–BICC1 as the most recurrent fusion in CHOL (5.6% of cholangiocarcinoma samples), with FGFR2 being a candidate druggable target PMID:29617662

Subtypes

  • Intrahepatic CCA (iCCA / IHCH): Enriched for IDH1/IDH2 mutations, FGFR2 fusions, BAP1 loss, ARID1A mutations; small-duct iCCA arises on chronic liver disease background; large-duct iCCA enriched for KRAS/TP53/TGF-β pathway.
  • Extrahepatic CCA (eCCA / EHCH): Includes perihilar (Klatskin) and distal subtypes; enriched for KRAS, TP53, SMAD4; higher ERBB2 alteration frequency than iCCA.
  • Combined HCC-CCA: Shares HBV-integration oncogenic mechanism (TERT, MET) with both HCC and iCCA.

Therapeutic landscape

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:29420467

This page was processed by entity-page-writer on 2026-05-15. - PMID:29617662

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