Genomic spectra of biliary tract cancer
Sequencing 260 Japanese bile duct and gallbladder cancers showed that the three sites carry different mutations, that nearly 40% have a targetable change, and that gallbladder and extrahepatic tumours carry a heavier APOBEC mutation signature.
Overview
260 biliary tract cancers, including intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, were molecularly characterised. Gradient spectra of mutational signatures with a higher burden of the APOBEC-associated signature were observed in gallbladder cancer and extrahepatic cholangiocarcinoma. Thirty-two significantly altered genes, including ELF3, were identified, and nearly 40% of cases harboured targetable genetic alterations.
Gene fusions involving FGFR2 and PRKACA or PRKACB preferentially occurred in intrahepatic and extrahepatic cholangiocarcinoma respectively. The subgroup with the poorest prognosis had significant enrichment of hypermutated tumours and a characteristic elevation in the expression of immune checkpoint molecules.
- 32 significantly altered genes, including ELF3; nearly 40% of cases had a targetable alteration.
- APOBEC mutational signature heaviest in gallbladder cancer and extrahepatic cholangiocarcinoma.
- FGFR2 fusions occurred preferentially in intrahepatic cholangiocarcinoma, PRKACA/PRKACB fusions in extrahepatic tumours.
The paper that separated the biliary tree into molecular subtypes: FGFR2 and IDH belong to the intrahepatic ducts, while gallbladder cancer carries HER2, ELF3 and an APOBEC signature. Its hypermutated, checkpoint-high poor-prognosis group foreshadowed immunotherapy.
- Japanese cohort; gallbladder cancers were a minority of the 260.
- Targetable was defined by the 2015 drug landscape.
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