Gallbladder Cancer (GBC)

Overview

Gallbladder carcinoma; in the corpus it is grouped with extrahepatic cholangiocarcinoma (EHCH) as the “biliary” reference class.

hcc_msk_2024 — GBC cases used (with EHC) as a reference class for the hidden-genome classifier of intrahepatic cholangiocarcinoma, within the broader MSK biliary/HCC MSK-IMPACT cohort (2003–2022) PMID:38864854.

EHC/GBC class characterized by KRAS, SMAD4, and CDKN2A loss PMID:38864854.
Largest single-institution genomic characterization of gallbladder carcinoma (233 patients / 244 samples via MSK-IMPACT): most frequent oncogenic alterations are TP53 (63%), CDKN2A deletions (21%), SMAD4 (19%), ARID1A (18%), and ERBB2 (15%); SMAD4 and STK11 mutations independently associated with reduced OS in metastatic disease; 35% of patients harbored actionable alterations (OncoKB levels 1/3A/3B) and 18% received biomarker-directed therapy PMID:36228155
Whole-exome sequencing of 16 gallbladder carcinomas (8 discovery + 8 prevalence screen) showed TP53 as the dominant driver (44% combined), with PBRM1 in 25%. Absent IDH1/IDH2 and BAP1/ARID1A mutations contrast sharply with intrahepatic cholangiocarcinoma, supporting genetically distinct biology despite shared biliary origin. PMID:24185509
Desmoplastic stroma drives GBC progression via CAF-secreted SEMA7A (upregulated on stiff 16 kPa matrix through YAP1/WWTR1/TEAD1), which signals through ITGB1 on tumor cells to activate AKT1/EP300, promoting EMT and stemness; high stromal SEMA7A associated with lymph node metastasis and shorter OS in 86 patients PMID:24997986
Review includes gallbladder cancer (GBC) in its scope of hepatobiliary malignancies affected by gut-liver axis dysregulation; bile acid metabolic reprogramming and gut microbiota changes described for the broader biliary tract cancer spectrum that encompasses GBC. PMID:25608663

Used as a reference class to define biliary-class IHCH, which carries markedly worse OS than HCC-class IHC PMID:38864854.

This page was processed by crosslinker on 2026-05-14. - PMID:24185509

This page was processed by crosslinker on 2026-05-14. - PMID:24997986

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

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