SAN FRANCISCO—Intrahepatic cholangiocarcinoma (IHCCA), extrahepatic cholangiocarcinoma (EHCCA), and gallbladder carcinomas (GBCA) have a diverse landscape of clinically relevant genomic alterations (CRGA) that could lead to targeted drug therapy, a study (Abstract 231) presented this week at the 2015 Gastrointestinal Cancers Symposium has shown.

Because patients with IHCCA, EHCCA, and GBCA typically present at an advanced stage and systemic chemotherapy usually only provides patients with a modest benefit, researchers sought to investigate whether comprehensive genomic profiling (GCP) could identify CRGA.

For the study, researchers used DNA from 412 IHCCA, 57 EHCCA, and 85 GBCA samples and performed GCP. Patient characteristics were similar across all three cancer types. IHCCA and GBCA were more common in females than males, and vice versa for EHCCA.

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Results showed that all three tumor types had CDKN2B loss and ARID1A alterations. IHCCA had FGFR1-3 fusions and amplifications, IDH1/2 substitutions, BRAF substitutions, and MET amplification. EHCCA and GBCA featured ERBB2 amplifications and PI3KCA substitutions (GBCA > EHCCA). All three featured KRAS substitutions (EHCCA > IHCCA > GBCA).

The findings suggest that there are a variety of genomic alterations in biliary tract cancers that can be potential targets for drug therapy for patients with GBCA, IHCCA, and EHCCA.


  1. Ross JS, Wang K, Catenacci DVT, et al. Comprehensive genomic profiling of biliary tract cancers to reveal tumor-specific differences and genomic alterations. J Clin Oncol. 2015;33:(suppl 3; abstr 231).