Genomic Profiling of Biliary Tract Cancers: Comprehensive Assessment of Anatomic and Geographic Heterogeneity, Co‐Alterations and Outcomes

作者：Diamantis I. Tsilimigras, Hunter Stecko, Dimitrios Moris, Timothy M. Pawlik · 发表于：Journal of Surgical Oncology · 年份：2025 · DOI：10.1002/jso.28081 · 被引用次数：11 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Fibroblast Growth Factor Research、Gallbladder and Bile Duct Disorders

BACKGROUND: Biliary tract cancers (BTCs) represent distinct biological and genomic entities. Anatomic and geographic heterogeneity in genomic profiling of BTC subtypes, genomic co-alterations, and their impact on long-term outcomes are not well defined. METHODS: Genomic data to characterize alterations among patients with BTCs were derived from the AACR GENIE registry (v15.1) and other genomic data sets. Patterns of mutational co-occurrence, frequency of co-alterations, and their impact on long-term outcomes among BTC patients were examined. RESULTS: Alterations in IDH1 and FGFR2 genes were mostly noted among intrahepatic cholangiocarcinoma (iCCA) samples, TP53, ERBB2/HER2, and SMAD4 mutations were more frequent among gallbladder cancer (GBC) samples while extrahepatic cholangiocarcinoma (eCCA) more commonly harbored KRAS mutations (all Q < 0.001). Alterations in IDH1 and FGFR2 genes were more frequent among iCCA samples from Western vs. Eastern populations, while KRAS, SMAD4, and ERBB2 mutations were more commonly observed among Eastern populations(all Q < 0.05). FGFR2 gene was frequently co-mutated with BAP1 (log2OR: 1.55, Q < 0.001), while IDH1 gene was commonly co-mutated with PBRM1 (log2OR: 1.09, Q < 0.001). Co-alteration rate among patients with IDH1-mutant iCCAs, FGFR2-rearranged iCCAs, KRAS-mutant eCCA, and HER2-mutant GBCs were 80.8%, 85.2%, 76.7%, and 100%, respectively. Among patients with iCCA and FGFR2 fusions/rearrangements, harboring co-alterations in the TP53 ...