Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets

Journal of Gastrointestinal Oncology
Benjamin A WeinbergMichael A Morse

Abstract

Biliary tract cancers (BTCs) are a heterogeneous group of aggressive, rare malignancies with limited standard chemotherapeutic options for advanced disease. Recent studies have demonstrated potential novel biliary cancer targets and a possible role for immunotherapy in the treatment of patients with this disease. Intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC), and gallbladder carcinoma (GBC) are frequently grouped together in clinical trials despite differences in tumor biology. To further investigate tumor biology differences, we profiled 1,502 BTCs using next-generation sequencing (NGS), immunohistochemistry, in situ hybridization, and RNA sequencing. IHCCs had higher rates of IDH1, BAP1, and PBRM1 mutations and FGFR2 fusions; EHCCs had higher rates of KRAS, CDKN2A, and BRCA1 mutations; and GBCs had higher rates of homologous recombination repair deficiency and Her2/neu overexpression and amplification. IHCCs and GBCs had higher rates of potential positive predictive biomarkers for immune checkpoint inhibition (PD-L1 expression, high microsatellite instability, and high tumor mutational burden) than EHCCs. These findings support clinical molecular profiling of BTCs to inform potential therapeut...Continue Reading

Citations

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