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A large commercial sequencing series of 554 biliary cancers, including 85 gallbladder tumours, showed that gallbladder cancer has HER2 changes in about one in six and almost no IDH or FGFR changes, the mirror image of intrahepatic bile duct cancer.
Hybrid capture-based comprehensive genomic profiling was performed for 412 intrahepatic cholangiocarcinomas, 57 extrahepatic cholangiocarcinomas and 85 gallbladder carcinomas, and the mutational profile was correlated with outcomes of standard and experimental therapies for 321 patients. In gallbladder carcinoma the most frequent alterations were TP53 (59%), CDKN2A/B (19%), ARID1A (13%) and ERBB2 (16%); in intrahepatic tumours TP53 (27%), CDKN2A/B (27%), KRAS (22%), ARID1A (18%) and IDH1 (16%); in extrahepatic tumours KRAS (42%), TP53 (40%), CDKN2A/B (17%) and SMAD4 (21%).
FGFR (11%) and IDH mutations (20%) were mostly limited to intrahepatic tumours and appeared mutually exclusive. TP53 and KRAS mutations predicted shorter survival in intrahepatic disease, FGFR2 alterations better survival, and patients with FGFR alterations had superior survival on FGFR-targeted therapy than on standard regimens (P = 0.006).
The clearest early head-to-head of the three biliary sites on one platform: for gallbladder cancer it made HER2 the target to test for and showed that IDH and FGFR inhibitors would rarely apply.
Shares ARID1A, SMAD4, MD Anderson Cancer Center, TP53.
Shares IDH1 / IDH2, FGFR2, HER2, Biliary tract cancer (cholangiocarcinoma).
Shares Cancer, ARID1A, SMAD4, Gallbladder cancer.
Shares Extrahepatic cholangiocarcinoma (perihilar and distal), Intrahepatic cholangiocarcinoma, Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
Shares Extrahepatic cholangiocarcinoma (perihilar and distal), Intrahepatic cholangiocarcinoma, Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.