Hepatocellular Carcinoma (HCC)

Overview

Primary liver cancer of hepatocellular origin.

Cohorts in the corpus

  • hcc_msk_2024 — HCC cases used as a training reference class for the hidden-genome classifier of intrahepatic cholangiocarcinoma, within a 1,370-patient MSK biliary/HCC MSK-IMPACT cohort (2003–2022) PMID:38864854.

Recurrent alterations

  • HCC reference class characterized by TERT alterations; “HCC-class” IHCH (IHC tumors with >90% HCC homology, 5.7%) likewise exhibit TERT alterations PMID:38864854.
  • cfDNA profiling via MSK-ACCESS (129-gene panel) detects alterations in 92.2% of advanced HCC patients (N=51); most frequently mutated genes: TERT promoter 57%, TP53 47%, CTNNB1 37%, ARID1A 18%, TSC2 14% PMID:37769223.
  • Plasma-tissue concordance 92.5% in matched samples; 27% of paired samples harbored cfDNA-exclusive alterations, of which 40% were OncoKB actionable PMID:37769223.
  • WNT-beta-catenin pathway altered in 45% and PI3K-AKT-mTOR pathway in 25% of HCC cfDNA cases; actionable TSC1/TSC2 alterations in 18% PMID:37769223.
  • Genomic review identified TERT promoter mutations, CTNNB1, and TP53 as top recurrent alterations in HCC with Wnt and mTOR as key therapeutic pathways PMID:22634756
  • Narrative review cataloguing HCC driver genes (TERT promoter ~59%, TP53 ~30%, CTNNB1 ~30%); TERT promoter mutations are the earliest recurrent somatic alteration, present in ~25% of cirrhotic preneoplastic nodules; mTOR pathway disrupted in 40–50% of HCC; mapped alterations to targeted therapy trials (sorafenib, tivantinib, everolimus, refametinib) PMID:24735922
  • Comprehensive review (n=1,289 WES patients) identified TERT promoter mutation (54%), CTNNB1 (29%), and TP53 (28%) as the most frequent somatic drivers; ~25% of HCCs harbour potentially targetable alterations; sorafenib and lenvatinib are first-line standards with regorafenib, cabozantinib, and ramucirumab (AFP≥400 ng/ml) as approved second-line options PMID:24798001
  • Narrative review notes overlap of HCC with cholangiocarcinoma (combined hepatocellular-cholangiocarcinoma); HBV DNA integration near TERT, MET, ALKBH5, and FAT2 is a shared oncogenic mechanism across HBV-associated HCC and iCCA PMID:25526346.
  • Review references HCC in the context of differentiating CCA from HCC: oral microbiota three-bacterial-biomarker classifier (AUC=0.981) distinguishes iCCA from HCC; BA-panel diagnostics also outperform CA19-9 for CCA vs HCC; prolonged broad-spectrum antibiotic use correlates with reduced survival in HCC patients on anti-PD-1 therapy. PMID:25608663
  • Whole-exome sequencing of 243 European HCC identified 161 putative driver genes in 11 pathways; TERT activation (60%), WNT/β-catenin (54%), PI3K/AKT/mTOR (51%), and TP53/cell-cycle (49%) are most frequent; 28% of HCC harbor FDA-targetable alterations; CDKN2A inactivation and FGF3/4/19/CCND1 amplification independently predict poor overall survival; two novel mutational signatures 23 and 24 discovered (signature 24 linked to aflatoxin B1/HBV) PMID:25822088
  • PIPseq cohort included hepatocellular carcinoma cases; UGT1A1 homozygous *28 (TA)7TAA allele identified as pharmacogenomic flag for irinotecan/SN-38 toxicity PMID:28007021
  • Pan-cancer aneuploidy study placed HCC in the epithelial arm-level cluster (alongside LUAD and BRCA) defined by 1q gain; HCC arm-level alteration patterns were used in the per-tumor-type aneuploidy analysis PMID:29622463

Subtypes

Therapeutic landscape

  • HCC-class IHC has markedly better OS than biliary-class IHC, independent of FGFR2/IDH1 alterations PMID:38864854.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22634756

This page was processed by crosslinker on 2026-05-14. - PMID:24735922

This page was processed by crosslinker on 2026-05-14. - PMID:24798001

This page was processed by crosslinker on 2026-05-14. - PMID:25526346

This page was processed by crosslinker on 2026-05-14. - PMID:25608663

This page was processed by crosslinker on 2026-05-14. - PMID:25822088

This page was processed by crosslinker on 2026-05-14. - PMID:28007021

This page was processed by wiki-cli on 2026-05-14. - PMID:29622463

This page was processed by wiki-cli on 2026-05-15.