4009 Background: Intrahepatic cholangiocarcinoma (IHCCA), extrahepatic cholangiocarcinoma (EHCCA) and gallbladder carcinomas (GBCA) typically present at an advanced stage and chemotherapy provides only modest benefit in most cases. We queried whether comprehensive genomic profiling (GCP) of IHCCA, EHCCA and GBCA would reveal distinctive patterns of genomic alterations (GA) and identify clinically relevant GA (CRGA) that could lead to targeted therapies. Methods: DNA was extracted from 412 IHCCA, 57 EHCCA and 85 GBCA. CGP was performed on hybridization-captured libraries to a mean coverage depth of > 600X for 236 cancer-related genes. The CGP assay included base substitutions, INDELs, copy number alterations and fusions/rearrangements. CRGA were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: Patient characteristics were similar for all three tumor types. IHCCA and GBCa were more common in females and EHCCA were more common males. Findings in th...