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Profiling 1,502 biliary cancers on one commercial platform, gallbladder tumours stood out for HER2 overexpression and amplification and for defects in homologous recombination repair, and, with intrahepatic tumours, for more immunotherapy markers than extrahepatic disease.
1,502 biliary tract cancers were profiled using next-generation sequencing, immunohistochemistry, in situ hybridisation and RNA sequencing to compare intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder carcinoma, which are frequently grouped together in trials despite differences in tumour biology.
Intrahepatic tumours had higher rates of IDH1, BAP1 and PBRM1 mutations and FGFR2 fusions; extrahepatic tumours higher rates of KRAS, CDKN2A and BRCA1 mutations; and gallbladder carcinomas higher rates of homologous recombination repair deficiency and HER2 overexpression and amplification. Intrahepatic and gallbladder tumours had higher rates of potential positive predictive biomarkers for immune checkpoint inhibition (PD-L1 expression, high microsatellite instability and high tumour mutational burden) than extrahepatic tumours.
The largest single-platform comparison; the abstract gives directions rather than percentages, so the figures on OnCo come from the other cohorts, but it supports testing gallbladder cancer for HER2, repair defects and immunotherapy markers.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), HER2.
Shares Caris Life Sciences, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Homologous recombination deficiency (HRD), BRCA1 / BRCA2 (HRD).
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), HER2.
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), HER2, Gallbladder cancer.
Shares BRCA1 / BRCA2 (HRD), HER2, Gallbladder cancer.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).