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DNA extracted from formalin-fixed paraffin-embedded tumor and paired nontumor tissues from PSC and BTC specimens was analyzed with copy number analysis, variant calling, and filtering. Fifty-three candidate cancer genes with 123 nonsynonymous alterations were found; subsets included novel BTC genes and actionable targets, with pathway alterations linked to reduced overall survival.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/whole-exome-sequencing-reveals-novel-cancer-genes-and-actionable-targets-in-biliary-tract-cancers-in-primary-sclerosing-cholangitis-visual-abstract/332203/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/whole-exome-sequencing-reveals-novel-cancer-genes-and-actionable-targets-in-biliary-tract-cancers-in-primary-sclerosing-cholangitis-visual-abstract/332203.png","ImageObject",300,407,{"name":92,"@type":93},"Maeve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main goal of using whole-exome sequencing in this study?","Question",{"text":112,"@type":113},"To characterize genomic alterations in BTC tumors associated with primary sclerosing cholangitis and to identify actionable cancer targets through pathway analyses and therapy annotation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were the DNA samples and sequencing analyses performed?",{"text":117,"@type":113},"DNA was extracted from formalin-fixed, paraffin-embedded tumor and paired nontumor tissue from 52 specimens, followed by whole-exome sequencing, copy number analysis, variant calling, and filtering before pathway assessment.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the key findings regarding cancer genes and actionable targets?",{"text":121,"@type":113},"The study identified 53 candidate cancer genes and numerous nonsynonymous alterations, including genes not previously implicated in BTC, and actionable alterations such as ERBB2, MDM2, and FGFR3, with pathway changes associated with reduced overall survival.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},332203,1790580479,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},5909877438554,"https://ap-avatar.wpscdn.com/avatar/5600025385ad2bf12a7?_k=1778553567797529272","Whole-exome sequencing reveals novel cancer genes and actionable targets in biliary tract cancers in primary  \nsclerosing cholangitis  \nVISUAL ABSTRACT  \nDOI: 10.1097/HC9.0000000000000461  \nO R IG INAL ART ICL E  \nWhole-exome sequencing reveals novel cancer genes and actionable targets in biliary tract cancers in primary sclerosing cholangitis  \nMarit M. Grimsrud 1,2,3  | Michael Forster4  | Benjamin Goeppert5,6,7  | Georg Hemmrich-Stanisak4  | Irmi Sax8 | Krzysztof Grzyb9  |  \nPeder R. Braadland 1,2,3  | Alphonse Charbel5  | Carmen Metzger5  | Thomas Albrecht5  | Tim Alexander Steiert4  | Matthias Schlesner8  | Michael P. Manns10  | Arndt Vogel10  | Sheraz Yaqub2, 11  |  \nTom H. Karlsen 1,2,3, 12  | Peter Schirmacher5  | Kirsten M. Boberg 1,2,3,12  | Andre Franke4  | Stephanie Roessler5  | Trine Folseraas 1,2,3, 12   \n1Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway  \n2Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway  \n3Research Institute of Internal Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway 4Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany  \n5Institute of Pathology, University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany 6Institute of Pathology, Hospital RKH Kliniken Ludwigsburg, Ludwigsburg, Germany  \n7Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland  \n8Biomedical Informatics, Data Mining and Data Analytics, University of Augsburg, Augsburg, Germany 9Department of Pathology, Oslo University Hospital, Oslo, Norway  \n10Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany 11Department of Hepatobiliary Surgery, Oslo University Hospital, Oslo, Norway  \n12Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway  \nCorrespondence  \nTrine Folseraas, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Postboks 4950 Nydalen, Oslo N-0424, Norway.  \nEmail: [trine.folseraas@medisin.uio. no](trine.folseraas@medisin.uio. no)  \n\n|  | Abstract |  |\n| --- | --- | --- |\n|  | Background: People with primary sclerosing cholangitis (PSC) have a 20% lifetime risk of biliary tract cancer (BTC) . Using whole-exome sequencing, we characterized genomic alterations in tissue samples from BTC with underlying PSC. |  |\n|  |  |  |\n\nAbbreviations: AF, allele frequency; AJCC, American Joint Committee on Cancer classification; BTC, biliary tract cancer; CCA, cholangiocarcinoma; CISH, chromogenin-situ-hybridization; CNV, copy number variation; FFPE, formalin-fixed paraffin-embedded; iCCA, intrahepatic cholangiocarcinoma; IHC, immunohistochemistry; NOS, not otherwise specified; PSC, primary sclerosing cholangitis; PSC-BTC, primary sclerosing cholangitis-associated biliary tract cancer; TMA, tissue microarray.  \nMarit M. Grimsrud and Michael Forster contributed equally to this work and therefore share the first authorship.  \nStephanie Roessler and Trine Folseraas contributed equally to this work and therefore share the last authorship.  \nSupplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.hepcommjournal.com.  \n-- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- -  \nThis is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share ","cbCaie0bCfsZ9jn1","https://ap.wps.com/l/cbCaie0bCfsZ9jn1","pdf",1956434,17,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions","[{\"question\":\"What was the main goal of using whole-exome sequencing in this study?\",\"answer\":\"To characterize genomic alterations in BTC tumors associated with primary sclerosing cholangitis and to identify actionable cancer targets through pathway analyses and therapy annotation.\"},{\"question\":\"How were the DNA samples and sequencing analyses performed?\",\"answer\":\"DNA was extracted from formalin-fixed, paraffin-embedded tumor and paired nontumor tissue from 52 specimens, followed by whole-exome sequencing, copy number analysis, variant calling, and filtering before pathway assessment.\"},{\"question\":\"What were the key findings regarding cancer genes and actionable targets?\",\"answer\":\"The study identified 53 candidate cancer genes and numerous nonsynonymous alterations, including genes not previously implicated in BTC, and actionable alterations such as ERBB2, MDM2, and FGFR3, with pathway changes associated with reduced overall survival.\"}]","Whole-exome sequencing reveals novel cancer genes and actionable targets in biliary tract cancers in primary sclerosing cholangitis - Visual Abstract | PDF",1789997298,43]