{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:41:49Z","timestamp":1792636909407,"version":"4.5.0"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Surgical Oncology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Biliary tract cancers (BTCs) represent distinct biological and genomic entities. Anatomic and geographic heterogeneity in genomic profiling of BTC subtypes, genomic co\u2010alterations, and their impact on long\u2010term outcomes are not well defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010occurrence, frequency of co\u2010alterations, and their impact on long\u2010term outcomes among BTC patients were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alterations in <jats:italic>IDH1<\/jats:italic> and <jats:italic>FGFR2<\/jats:italic> genes were mostly noted among intrahepatic cholangiocarcinoma (iCCA) samples, <jats:italic>TP53<\/jats:italic>, <jats:italic>ERBB2\/HER2<\/jats:italic>, and <jats:italic>SMAD4<\/jats:italic> mutations were more frequent among gallbladder cancer (GBC) samples while extrahepatic cholangiocarcinoma (eCCA) more commonly harbored <jats:italic>KRAS<\/jats:italic> mutations (all <jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.001). Alterations in <jats:italic>IDH1<\/jats:italic> and <jats:italic>FGFR2<\/jats:italic> genes were more frequent among iCCA samples from Western vs. Eastern populations, while <jats:italic>KRAS<\/jats:italic>, <jats:italic>SMAD4<\/jats:italic>, and <jats:italic>ERBB2<\/jats:italic> mutations were more commonly observed among Eastern populations(all <jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.05). <jats:italic>FGFR2<\/jats:italic> gene was frequently co\u2010mutated with <jats:italic>BAP1<\/jats:italic> (log2OR: 1.55, <jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.001), while <jats:italic>IDH1<\/jats:italic> gene was commonly co\u2010mutated with <jats:italic>PBRM1<\/jats:italic> (log2OR: 1.09, <jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.001). Co\u2010alteration rate among patients with <jats:italic>IDH1<\/jats:italic>\u2010mutant iCCAs, <jats:italic>FGFR2<\/jats:italic>\u2010rearranged iCCAs, <jats:italic>KRAS<\/jats:italic>\u2010mutant eCCA, and <jats:italic>HER2<\/jats:italic>\u2010mutant GBCs were 80.8%, 85.2%, 76.7%, and 100%, respectively. Among patients with iCCA and <jats:italic>FGFR2<\/jats:italic> fusions\/rearrangements, harboring co\u2010alterations in the <jats:italic>TP53<\/jats:italic> pathway or <jats:italic>PI3K<\/jats:italic> pathway correlated with worse overall survival (OS), while patients with <jats:italic>IDH1<\/jats:italic>\u2010mutant iCCA had worse OS when harboring co\u2010alterations in the cell cycle pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Marked genomic heterogeneity exists among patients with BTCs based on anatomic and geographic location. The overwhelming majority of BTC patients with clinically significant mutations had concurrent genomic co\u2010alterations. The current study highlights the molecular complexity of BTCs with multiple alterations that commonly co\u2010exist and could potentially be targeted to treat BTCs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jso.28081","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T12:04:07Z","timestamp":1736769847000},"page":"1352-1361","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genomic Profiling of Biliary Tract Cancers: Comprehensive Assessment of Anatomic and Geographic Heterogeneity, Co\u2010Alterations and Outcomes"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3676-9263","authenticated-orcid":false,"given":"Diamantis I.","family":"Tsilimigras","sequence":"first","affiliation":[{"name":"Department of Surgery Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter","family":"Stecko","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5276-0699","authenticated-orcid":false,"given":"Dimitrios","family":"Moris","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University Hospital Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-9870","authenticated-orcid":false,"given":"Timothy M.","family":"Pawlik","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center Columbus Ohio 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