{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T09:22:05Z","timestamp":1781169725125,"version":"3.54.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T00:00:00Z","timestamp":1597795200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) may exceed 20%, and BTC is currently the leading cause of death in patients with PSC. To open new avenues for management, we aimed to delineate clinically relevant genomic and pathological features of a large panel of PSC\u2010associated BTC (PSC\u2010BTC).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We analyzed formalin\u2010fixed, paraffin\u2010embedded tumor tissue from 186 patients with PSC\u2010BTC from 11 centers in eight countries with all anatomical locations included. We performed tumor DNA sequencing at 42 clinically relevant genetic loci to detect mutations, translocations, and copy number variations, along with histomorphological and immunohistochemical characterization. Regardless of the anatomical localization, PSC\u2010BTC exhibited a uniform molecular and histological characteristic similar to extrahepatic cholangiocarcinoma. We detected a high frequency of genomic alterations typical of extrahepatic cholangiocarcinoma, such as <jats:italic toggle=\"yes\">TP53<\/jats:italic> (35.5%), <jats:italic toggle=\"yes\">KRAS<\/jats:italic> (28.0%), <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic> (14.5%), and <jats:italic toggle=\"yes\">SMAD4<\/jats:italic> (11.3%), as well as potentially druggable mutations (e.g., <jats:italic toggle=\"yes\">HER2<\/jats:italic>\/<jats:italic toggle=\"yes\">ERBB2<\/jats:italic>). We found a high frequency of nontypical\/nonductal histomorphological subtypes (55.2%) and of the usually rare BTC precursor lesion, intraductal papillary neoplasia (18.3%).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Genomic alterations in PSC\u2010BTC include a significant number of putative actionable therapeutic targets. Notably, PSC\u2010BTC shows a distinct extrahepatic morpho\u2010molecular phenotype, independent of the anatomical location of the tumor. These findings advance our understanding of PSC\u2010associated cholangiocarcinogenesis and provide strong incentives for clinical trials to test genome\u2010based personalized treatment strategies in PSC\u2010BTC.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31110","type":"journal-article","created":{"date-parts":[[2020,1,11]],"date-time":"2020-01-11T07:25:37Z","timestamp":1578727537000},"page":"1253-1266","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":62,"title":["Genomic Characterization of Cholangiocarcinoma in Primary Sclerosing Cholangitis Reveals Therapeutic Opportunities"],"prefix":"10.1097","volume":"72","author":[{"given":"Benjamin","family":"Goeppert","sequence":"first","affiliation":[{"name":"Department of General Pathology, Institute of Pathology,University Hospital Heidelberg,Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine","family":"Folseraas","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center Department of Transplantation Medicine,Division of Surgery, Inflammatory Medicine and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"},{"name":"Institute of Clinical Medicine,Faculty of Medicine,University of Oslo,Oslo,Norway"},{"name":"Research Institute of Internal Medicine,Division of Surgery, Inflammatory Medicine and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"},{"name":"K.G. Jebsen Inflammation Research Center,Institute of Clinical Medicine,Faculty of Medicine,University of Oslo,Oslo,Norway"},{"name":"Section for Gastroenterology,Department of Transplantation Medicine,Division of Surgery, Inflammatory Medicine and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Roessler","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Institute of Pathology,University Hospital Heidelberg,Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kloor","sequence":"additional","affiliation":[{"name":"Department of Applied Tumor Biology,Institute of Pathology,University of Heidelberg,Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Lena","family":"Volckmar","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Institute of Pathology,University Hospital Heidelberg,Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Endris","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Institute of Pathology,University Hospital Heidelberg,Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Buchhalter","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Institute of Pathology,University Hospital Heidelberg,Heidelberg,Germany"},{"name":"Institute of Pathology, Omics IT and Data Management Core Facility, German Cancer Research Center (DKFZ),Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albrecht","family":"Stenzinger","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Institute of Pathology,University Hospital Heidelberg,Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Grzyb","sequence":"additional","affiliation":[{"name":"Department of Pathology,Oslo University Hospital,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marit M.","family":"Grimsrud","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center Department of Transplantation Medicine,Division of Surgery, Inflammatory Medicine and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"},{"name":"Institute of Clinical Medicine,Faculty of Medicine,University of Oslo,Oslo,Norway"},{"name":"Research Institute of Internal Medicine,Division of Surgery, Inflammatory Medicine and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Gornicka","sequence":"additional","affiliation":[{"name":"Department of Pathology,Medical University of Warsaw,Warsaw,Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"von Seth","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Karolinska Institutet,Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Center for Liver Research,NIHR Birmingham Liver Biomedical Research Unit,University of Birmingham,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology,Christian\u2010Albrechts University,Kiel,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel N.","family":"Gotthardt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV,University Hospital Heidelberg,Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianeb","family":"Mehrabi","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery,University of Heidelberg,Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Verheij","sequence":"additional","affiliation":[{"name":"Department of Pathology,Academic Medical Center,Amsterdam,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Arola","sequence":"additional","affiliation":[{"name":"Department of Pathology,Haartman Institute and Huslab,Helsinki University 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Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Mazza","sequence":"additional","affiliation":[{"name":"Division of Medicine,Institute for Liver and Digestive Health Royal Free Hospital,University College London,London,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon M.","family":"Hirschfield","sequence":"additional","affiliation":[{"name":"Center for Liver Research,NIHR Birmingham Liver Biomedical Research Unit,University of Birmingham,Birmingham,United Kingdom"},{"name":"University Hospital Birmingham,NHS Foundation Trust,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyriel Y.","family":"Ponsioen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Academic Medical Center,Amsterdam,the 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Hamburg\u2010Eppendorf,Hamburg,Germany"},{"name":"Martin Zeitz Center for Rare Diseases,University Medical Center Hamburg\u2010Eppendorf,Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Manns","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology,Hannover Medical School,Hannover,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martti","family":"F\u00e4rkkil\u00e4","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology,Helsinki University Hospital,Helsinki,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology,Hannover Medical School,Hannover,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"International PSC Study 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