{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:20:20Z","timestamp":1780582820232,"version":"3.54.1"},"reference-count":114,"publisher":"Georg Thieme Verlag KG","issue":"04","funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"crossref","award":["1.A.424.24F,T\u00e9l\u00e9vie 7.8505.21"],"award-info":[{"award-number":["1.A.424.24F,T\u00e9l\u00e9vie 7.8505.21"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005026","name":"Stichting Tegen Kanker","doi-asserted-by":"crossref","award":["2018-078"],"award-info":[{"award-number":["2018-078"]}],"id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005043","name":"Fonds Joseph Maisin","doi-asserted-by":"crossref","award":["2020-2021,2022-2023"],"award-info":[{"award-number":["2020-2021,2022-2023"]}],"id":[{"id":"10.13039\/501100005043","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Liver Dis"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:p>Biliary tract cancer is a devastating malignancy of the bile ducts and gallbladder with a dismal prognosis. The study of precancerous lesions has received considerable attention and led to a histopathological classification which, in some respects, remains an evolving field. Consequently, increasing efforts have been devoted to characterizing the molecular pathogenesis of the precursor lesions, with the aim of better understanding the mechanisms of tumor progression, and with the ultimate goal of meeting the challenges of early diagnosis and treatment. This review delves into the molecular mechanisms that initiate and promote the development of precursor lesions of intra- and extrahepatic cholangiocarcinoma and of gallbladder carcinoma. It addresses the genomic, epigenomic, and transcriptomic landscape of these precursors and provides an overview of animal and organoid models used to study them. In conclusion, this review summarizes the known molecular features of precancerous lesions in biliary tract cancer and highlights our fragmentary knowledge of the molecular pathogenesis of tumor initiation.<\/jats:p>","DOI":"10.1055\/a-2207-9834","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T01:22:49Z","timestamp":1699579369000},"page":"472-484","source":"Crossref","is-referenced-by-count":6,"title":["Biliary Tract Cancer: Molecular Biology of Precursor Lesions"],"prefix":"10.1055","volume":"43","author":[{"given":"F\u00e1tima","family":"Manzano-N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"de Duve Institute, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Prates Tiago Aguilar","sequence":"additional","affiliation":[{"name":"de Duve Institute, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Sempoux","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Lausanne University Hospital CHUV, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric P.","family":"Lemaigre","sequence":"additional","affiliation":[{"name":"de Duve Institute, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"issue":"03","key":"ref1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1186\/s12885-022-10286-z","article-title":"Epidemiologic patterns of biliary tract cancer in the United States: 2001-2015","volume":"22","author":"J Koshiol","year":"2022","journal-title":"BMC Cancer"},{"key":"ref3","first-page":"283","volume-title":"Carcinoma of the gallbladder","author":"J C Roa","year":"2019","edition":"5th ed."},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41572-022-00398-y","article-title":"Gallbladder cancer","volume":"8","author":"J C Roa","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"ref5","first-page":"99","article-title":"Gallbladder cancer: epidemiology and outcome","volume":"6","author":"R Hundal","year":"2014","journal-title":"Clin Epidemiol"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1097\/SLA.0000000000004482","article-title":"Pancreatobiliary maljunction-associated gallbladder cancer is as common in the West, shows distinct clinicopathologic characteristics and offers an invaluable model for anatomy-induced reflux-associated physio-chemical carcinogenesis","volume":"276","author":"T Muraki","year":"2022","journal-title":"Ann Surg"},{"key":"ref7","first-page":"254","volume-title":"Intrahepatic cholangiocarcinoma","author":"Y Nakanuma","year":"2019","edition":"5th ed."},{"issue":"09","key":"ref8","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: the next horizon in mechanisms and management","volume":"17","author":"J M Banales","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"03","key":"ref9","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/hep.510310302","article-title":"Functional heterogeneity of the intrahepatic biliary epithelium","volume":"31","author":"N Kanno","year":"2000","journal-title":"Hepatology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-pathmechdis-012418-013013","article-title":"Development of the intrahepatic and extrahepatic biliary tract: a framework for understanding congenital diseases","volume":"15","author":"F P Lemaigre","year":"2020","journal-title":"Annu Rev Pathol"},{"issue":"01","key":"ref11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.stem.2019.04.004","article-title":"Single-cell analysis of the liver epithelium reveals dynamic heterogeneity and an essential role for YAP in homeostasis and regeneration","volume":"25","author":"B J Pepe-Mooney","year":"2019","journal-title":"Cell Stem Cell"},{"issue":"05","key":"ref12","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.jcmgh.2021.01.009","article-title":"Sox9(EGFP) defines biliary epithelial heterogeneity downstream of Yap activity","volume":"11","author":"D Y Tulasi","year":"2021","journal-title":"Cell Mol Gastroenterol Hepatol"},{"issue":"04","key":"ref13","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/hep4.1854","article-title":"Single-cell, single-nucleus, and spatial RNA sequencing of the human liver identifies cholangiocyte and mesenchymal heterogeneity","volume":"6","author":"T S Andrews","year":"2022","journal-title":"Hepatol Commun"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1126\/science.aaz6964","article-title":"Cholangiocyte organoids can repair bile ducts after transplantation in the human liver","volume":"371","author":"F Sampaziotis","year":"2021","journal-title":"Science"},{"issue":"01","key":"ref15","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41572-021-00300-2","article-title":"Cholangiocarcinoma","volume":"7","author":"P J Brindley","year":"2021","journal-title":"Nat Rev Dis Primers"},{"issue":"21","key":"ref16","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.3390\/cancers13215257","article-title":"Gallbladder cancer: current insights in genetic alterations and their possible therapeutic implications","volume":"13","author":"H Kuipers","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"21","key":"ref17","doi-asserted-by":"crossref","first-page":"5358","DOI":"10.3390\/cancers14215358","article-title":"Pathologies of precursor lesions of biliary tract carcinoma","volume":"14","author":"Y Nakanuma","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"12","key":"ref18","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.3390\/jcm9123991","article-title":"Intraductal papillary neoplasm of bile duct: updated clinicopathological characteristics and molecular and genetic alterations","volume":"9","author":"Y Nakanuma","year":"2020","journal-title":"J Clin Med"},{"issue":"02","key":"ref19","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3390\/diagnostics12020341","article-title":"Precursor lesions of gallbladder carcinoma: disease concept, pathology, and genetics","volume":"12","author":"Y Fukumura","year":"2022","journal-title":"Diagnostics (Basel)"},{"issue":"01","key":"ref20","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1053\/gast.1996.v111.pm8698204","article-title":"Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression","volume":"111","author":"I Roa","year":"1996","journal-title":"Gastroenterology"},{"issue":"05","key":"ref21","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/1097-0142(19800301)45:5<919::AID-CNCR2820450514>3.0.CO;2-4","article-title":"The precursor lesions of invasive gallbladder carcinoma. Hyperplasia, atypical hyperplasia and carcinoma in situ","volume":"45","author":"J Albores-Saavedra","year":"1980","journal-title":"Cancer"},{"issue":"07","key":"ref22","first-page":"989","article-title":"Intestinal metaplasia-dysplasia-carcinoma sequence of the gallbladder","volume":"36","author":"H Yamagiwa","year":"1986","journal-title":"Acta Pathol Jpn"},{"issue":"01","key":"ref23","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/his.14360","article-title":"Dysplasia and carcinoma of the gallbladder: pathological evaluation, sampling, differential diagnosis and clinical implications","volume":"79","author":"J C Roa","year":"2021","journal-title":"Histopathology"},{"issue":"01","key":"ref24","first-page":"26","article-title":"Metaplastic changes in chronic cholecystitis: implications for early diagnosis and surgical intervention to prevent the gallbladder metaplasia-dysplasia-carcinoma sequence","volume":"6","author":"C Seretis","year":"2014","journal-title":"J Clin Med Res"},{"issue":"03","key":"ref25","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s12253-014-9886-3","article-title":"Pathology of gallbladder carcinoma: current understanding and new perspectives","volume":"21","author":"M M Bal","year":"2015","journal-title":"Pathol Oncol Res"},{"issue":"03","key":"ref26","doi-asserted-by":"crossref","first-page":"386","DOI":"10.5858\/2005-129-386-PPOGDA","article-title":"Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens","volume":"129","author":"S Mukhopadhyay","year":"2005","journal-title":"Arch Pathol Lab Med"},{"key":"ref27","first-page":"273","volume-title":"Biliary intraepithelial neoplasia","author":"O Basturk","year":"2019","edition":"5th ed."},{"issue":"03","key":"ref28","doi-asserted-by":"crossref","first-page":"147","DOI":"10.32074\/1591-951X-251","article-title":"Benign biliary neoplasms and biliary tumor precursors","volume":"113","author":"S Sarcognato","year":"2021","journal-title":"Pathologica"},{"issue":"10","key":"ref29","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1002\/1097-0142(19821115)50:10<2226::AID-CNCR2820501043>3.0.CO;2-3","article-title":"Relation of adenoma to carcinoma in the gallbladder","volume":"50","author":"S Kozuka","year":"1982","journal-title":"Cancer"},{"key":"ref30","first-page":"271","volume-title":"Pyloric gland adenoma of the gallbladder","author":"O Basturk","year":"2019","edition":"5th ed."},{"key":"ref31","first-page":"271","volume-title":"Intracholecystic papillary neoplasm","author":"O Basturk","year":"2019","edition":"5th ed."},{"issue":"01","key":"ref32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1186\/s12876-022-02454-z","article-title":"Natural history of intracholecystic papillary neoplasm (ICPN): a rare case of ICPN whose natural history was closely followed by ultrasound","volume":"22","author":"D Koike","year":"2022","journal-title":"BMC Gastroenterol"},{"issue":"09","key":"ref33","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1097\/PAS.0000000000000882","article-title":"Reflux-associated cholecystopathy: analysis of 76 gallbladders from patients with supra-Oddi union of the pancreatic duct and common bile duct (pancreatobiliary maljunction) elucidates a specific diagnostic pattern of mucosal hyperplasia as a prelude to carcinoma","volume":"41","author":"T Muraki","year":"2017","journal-title":"Am J Surg Pathol"},{"key":"ref34","first-page":"279","volume-title":"Intraductal papillary neoplasms of the bile ducts","author":"Y Nakanuma","year":"2019","edition":"5th ed."},{"issue":"10","key":"ref35","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.hpb.2021.03.004","article-title":"A clinicopathological reappraisal of intraductal papillary neoplasm of the bile duct (IPNB): a continuous spectrum with papillary cholangiocarcinoma in 181 curatively resected cases","volume":"23","author":"S Onoe","year":"2021","journal-title":"HPB (Oxford)"},{"issue":"12","key":"ref36","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.5858\/arpa.2022-0343-OA","article-title":"Tumoral intraductal neoplasms of the bile ducts comprise morphologically and genetically distinct entities","volume":"147","author":"T Wang","year":"2023","journal-title":"Arch Pathol Lab Med"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.humpath.2022.07.019","article-title":"Intraductal tubulopapillary neoplasms of the bile ducts: identity, clinicopathologic characteristics, and differential diagnosis of a distinct entity among intraductal tumors","volume":"132","author":"B Pehlivanoglu","year":"2023","journal-title":"Hum Pathol"},{"issue":"06","key":"ref38","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1093\/annonc\/mdu006","article-title":"A genetic model for gallbladder carcinogenesis and its dissemination","volume":"25","author":"S G Barreto","year":"2014","journal-title":"Ann Oncol"},{"issue":"03","key":"ref39","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/S1665-2681(19)32065-4","article-title":"TP53 abnormalities are frequent and early events in the sequential pathogenesis of gallbladder carcinoma","volume":"4","author":"M Moreno","year":"2005","journal-title":"Ann Hepatol"},{"issue":"04","key":"ref40","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/S0046-8177(96)90109-4","article-title":"p53 protein overexpression in gallbladder carcinoma and its precursor lesions: an immunohistochemical study","volume":"27","author":"I I Wistuba","year":"1996","journal-title":"Hum Pathol"},{"issue":"01","key":"ref41","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.1038\/s41467-021-25012-9","article-title":"Genomic characterization of co-existing neoplasia and carcinoma lesions reveals distinct evolutionary paths of gallbladder cancer","volume":"12","author":"J Lin","year":"2021","journal-title":"Nat Commun"},{"issue":"12","key":"ref42","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1038\/ng.2813","article-title":"Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas","volume":"45","author":"Y Jiao","year":"2013","journal-title":"Nat Genet"},{"issue":"08","key":"ref43","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/ng.3030","article-title":"Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway","volume":"46","author":"M Li","year":"2014","journal-title":"Nat Genet"},{"issue":"09","key":"ref44","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/ng.3375","article-title":"Genomic spectra of biliary tract cancer","volume":"47","author":"H Nakamura","year":"2015","journal-title":"Nat Genet"},{"issue":"05","key":"ref45","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.jhep.2018.01.009","article-title":"Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations","volume":"68","author":"C P Wardell","year":"2018","journal-title":"J Hepatol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.mrrev.2018.08.003","article-title":"Genetic landscape of gallbladder cancer: Global overview","volume":"778","author":"R Mehrotra","year":"2018","journal-title":"Mutat Res Rev Mutat Res"},{"issue":"02","key":"ref47","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jhep.2020.03.008","article-title":"Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma","volume":"73","author":"R Montal","year":"2020","journal-title":"J Hepatol"},{"issue":"04","key":"ref48","doi-asserted-by":"crossref","first-page":"733","DOI":"10.3390\/cancers13040733","article-title":"Molecular classification and tumor microenvironment characterization of gallbladder cancer by comprehensive genomic and transcriptomic analysis","volume":"13","author":"N Ebata","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"05","key":"ref49","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.jhep.2020.11.033","article-title":"Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes","volume":"74","author":"C Nepal","year":"2021","journal-title":"J Hepatol"},{"issue":"06","key":"ref50","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1097\/SLA.0000000000000495","article-title":"Sequential occurrence of preneoplastic lesions and accumulation of loss of heterozygosity in patients with gallbladder stones suggest causal association with gallbladder cancer","volume":"260","author":"K Jain","year":"2014","journal-title":"Ann Surg"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"e78636","DOI":"10.7554\/eLife.78636","article-title":"Gallbladder adenocarcinomas undergo subclonal diversification and selection from precancerous lesions to metastatic tumors","volume":"11","author":"M Kang","year":"2022","journal-title":"eLife"},{"issue":"01","key":"ref52","first-page":"19","article-title":"More frequent beta-catenin exon 3 mutations in gallbladder adenomas than in carcinomas indicate different lineages","volume":"61","author":"N Yanagisawa","year":"2001","journal-title":"Cancer Res"},{"issue":"06","key":"ref53","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1097\/00000478-200206000-00009","article-title":"Mutation and altered expression of beta-catenin during gallbladder carcinogenesis","volume":"26","author":"H J Chang","year":"2002","journal-title":"Am J Surg Pathol"},{"issue":"09","key":"ref54","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1097\/PAS.0000000000001117","article-title":"Pyloric gland adenoma (PGA) of the gallbladder: a unique and distinct tumor from PGAs of the stomach, duodenum, and pancreas","volume":"42","author":"C He","year":"2018","journal-title":"Am J Surg Pathol"},{"issue":"06","key":"ref55","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1097\/PAS.0000000000001237","article-title":"Intracholecystic papillary neoplasms are distinct from papillary gallbladder cancers: a clinicopathologic and exome-sequencing study","volume":"43","author":"M Akita","year":"2019","journal-title":"Am J Surg Pathol"},{"issue":"01","key":"ref56","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s12957-020-02072-7","article-title":"Intracholecystic papillary neoplasm arising in a patient with pancreaticobiliary maljunction: a case report","volume":"18","author":"T Iwasaki","year":"2020","journal-title":"World J Surg Oncol"},{"issue":"02","key":"ref57","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/PAI.0b013e3181f09179","article-title":"Mutations in the RAS\/RAF\/MAP kinase pathway commonly occur in gallbladder adenomas but are uncommon in gallbladder adenocarcinomas","volume":"19","author":"R K Pai","year":"2011","journal-title":"Appl Immunohistochem Mol Morphol"},{"issue":"01","key":"ref58","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1186\/s12885-021-09000-2","article-title":"Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study","volume":"21","author":"S Kawakami","year":"2021","journal-title":"BMC Cancer"},{"issue":"08","key":"ref59","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1245\/ASO.2003.02.014","article-title":"Progression of gene hypermethylation in gallstone disease leading to gallbladder cancer","volume":"10","author":"M G House","year":"2003","journal-title":"Ann Surg Oncol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"6126","DOI":"10.1158\/1078-0432.CCR-04-0579","article-title":"Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis","volume":"10","author":"T Takahashi","year":"2004","journal-title":"Clin Cancer Res"},{"issue":"01","key":"ref61","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/mc.20457","article-title":"Promoter methylation profile in preneoplastic and neoplastic gallbladder lesions","volume":"48","author":"P Garc\u00eda","year":"2009","journal-title":"Mol Carcinog"},{"issue":"11","key":"ref62","doi-asserted-by":"crossref","first-page":"14687","DOI":"10.1007\/s13277-016-5355-9","article-title":"Global methylation profiling to identify epigenetic signature of gallbladder cancer and gallstone disease","volume":"37","author":"P Sharma","year":"2016","journal-title":"Tumour Biol"},{"issue":"01","key":"ref63","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1868-7083-4-11","article-title":"DNA promoter methylation as a diagnostic and therapeutic biomarker in gallbladder cancer","volume":"4","author":"P Letelier","year":"2012","journal-title":"Clin Epigenetics"},{"issue":"06","key":"ref64","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1002\/hep.31585","article-title":"Epigenome-wide analysis of methylation changes in the sequence of gallstone disease, dysplasia, and gallbladder cancer","volume":"73","author":"J Br\u00e4gelmann","year":"2021","journal-title":"Hepatology"},{"issue":"02","key":"ref65","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.yexmp.2011.06.004","article-title":"The risk factor of gallbladder cancer: hyperplasia of mucous epithelium caused by gallstones associates with p16\/CyclinD1\/CDK4 pathway","volume":"91","author":"Z Feng","year":"2011","journal-title":"Exp Mol Pathol"},{"issue":"09","key":"ref66","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1002\/cncr.27955","article-title":"KRAS and GNAS mutations and p53 overexpression in biliary intraepithelial neoplasia and intrahepatic cholangiocarcinomas","volume":"119","author":"M Hsu","year":"2013","journal-title":"Cancer"},{"issue":"02","key":"ref67","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.humpath.2014.09.016","article-title":"Autophagy may occur at an early stage of cholangiocarcinogenesis via biliary intraepithelial neoplasia","volume":"46","author":"M Sasaki","year":"2015","journal-title":"Hum Pathol"},{"issue":"08","key":"ref68","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.humpath.2007.11.018","article-title":"Expression of cell cycle-related molecules in biliary premalignant lesions: biliary intraepithelial neoplasia and biliary intraductal papillary neoplasm","volume":"39","author":"Y Nakanishi","year":"2008","journal-title":"Hum Pathol"},{"issue":"03","key":"ref69","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/path.5514","article-title":"miRNA profiling of biliary intraepithelial neoplasia reveals stepwise tumorigenesis in distal cholangiocarcinoma via the miR-451a\/ATF2 axis","volume":"252","author":"M A Loeffler","year":"2020","journal-title":"J Pathol"},{"issue":"09","key":"ref70","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1111\/j.1478-3231.2007.01577.x","article-title":"Immunohistochemical analysis of the progression of flat and papillary preneoplastic lesions in intrahepatic cholangiocarcinogenesis in hepatolithiasis","volume":"27","author":"K Itatsu","year":"2007","journal-title":"Liver Int"},{"issue":"11","key":"ref71","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1038\/s41379-019-0306-9","article-title":"Targeted next-generation sequencing identifies distinct clinicopathologic and molecular entities of intraductal papillary neoplasms of the bile duct","volume":"32","author":"C Y Yang","year":"2019","journal-title":"Mod Pathol"},{"issue":"01","key":"ref72","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/path.5398","article-title":"Intraductal papillary neoplasms of the bile duct consist of two distinct types specifically associated with clinicopathological features and molecular phenotypes","volume":"251","author":"Y Aoki","year":"2020","journal-title":"J Pathol"},{"issue":"02","key":"ref73","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1136\/gutjnl-2020-322983","article-title":"Integrative analysis reveals early and distinct genetic and epigenetic changes in intraductal papillary and tubulopapillary cholangiocarcinogenesis","volume":"71","author":"B Goeppert","year":"2022","journal-title":"Gut"},{"issue":"06","key":"ref74","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/ng.2273","article-title":"Exome sequencing of liver fluke-associated cholangiocarcinoma","volume":"44","author":"C K Ong","year":"2012","journal-title":"Nat Genet"},{"issue":"12","key":"ref75","doi-asserted-by":"crossref","first-page":"e81706","DOI":"10.1371\/journal.pone.0081706","article-title":"GNAS and KRAS mutations are common in intraductal papillary neoplasms of the bile duct","volume":"8","author":"M Sasaki","year":"2013","journal-title":"PLoS One"},{"issue":"10","key":"ref76","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/j.1477-2574.2012.00504.x","article-title":"GNAS codon 201 mutations are uncommon in intraductal papillary neoplasms of the bile duct","volume":"14","author":"H Matthaei","year":"2012","journal-title":"HPB (Oxford)"},{"issue":"05","key":"ref77","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1111\/his.13125","article-title":"RNF43 mutation frequently occurs with GNAS mutation and mucin hypersecretion in intraductal papillary neoplasms of the bile duct","volume":"70","author":"J H Tsai","year":"2017","journal-title":"Histopathology"},{"issue":"12","key":"ref78","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1097\/PAS.0b013e3182986bb5","article-title":"GNAS Is frequently mutated in a specific subgroup of intraductal papillary neoplasms of the bile duct","volume":"37","author":"J H Tsai","year":"2013","journal-title":"Am J Surg Pathol"},{"issue":"09","key":"ref79","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1097\/PAS.0000000000001295","article-title":"The pathologic and genetic characteristics of the intestinal subtype of intraductal papillary neoplasms of the bile duct","volume":"43","author":"Y Nakanuma","year":"2019","journal-title":"Am J Surg Pathol"},{"issue":"12","key":"ref80","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1097\/PAS.0000000000001155","article-title":"Recurrent mutations in APC and CTNNB1 and activated Wnt\/beta-catenin signaling in intraductal papillary neoplasms of the bile duct: a whole exome sequencing study","volume":"42","author":"K Fujikura","year":"2018","journal-title":"Am J Surg Pathol"},{"issue":"03","key":"ref81","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1053\/j.gastro.2019.10.028","article-title":"Recurrent rearrangements in PRKACA and PRKACB in intraductal oncocytic papillary neoplasms of the pancreas and bile duct","volume":"158","author":"A D Singhi","year":"2020","journal-title":"Gastroenterology"},{"issue":"01","key":"ref82","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/modpathol.2013.112","article-title":"Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways","volume":"27","author":"A M Schlitter","year":"2014","journal-title":"Mod Pathol"},{"issue":"03","key":"ref83","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/his.12016","article-title":"Overexpression of enhancer of zeste homolog 2 and MUC1 may be related to malignant behaviour in intraductal papillary neoplasm of the bile duct","volume":"62","author":"M Sasaki","year":"2013","journal-title":"Histopathology"},{"issue":"11","key":"ref84","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.3390\/cancers13112742","article-title":"Whole exome sequencing of biliary tubulopapillary neoplasms reveals common mutations in chromatin remodeling genes","volume":"13","author":"C Gross","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"09","key":"ref85","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/S0046-8177(03)00337-X","article-title":"Molecular and immunohistochemical analysis of intraductal papillary neoplasms of the biliary tract","volume":"34","author":"S C Abraham","year":"2003","journal-title":"Hum Pathol"},{"issue":"02","key":"ref86","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jhep.2019.03.024","article-title":"Dynamics and predicted drug response of a gene network linking dedifferentiation with beta-catenin dysfunction in hepatocellular carcinoma","volume":"71","author":"C G\u00e9rard","year":"2019","journal-title":"J Hepatol"},{"issue":"06","key":"ref87","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.21873\/anticanres.15771","article-title":"DNMT1 expression and DNA methylation in intraductal papillary neoplasms of the bile duct","volume":"42","author":"R Doi","year":"2022","journal-title":"Anticancer Res"},{"issue":"05","key":"ref88","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.bbadis.2018.03.026","article-title":"Animal models of cholangiocarcinoma","volume":"1865","author":"E Loeuillard","year":"2019","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"05","key":"ref89","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.clinre.2018.04.008","article-title":"Animal models of cholangiocarcinoma: what they teach us about the human disease","volume":"42","author":"M Cadamuro","year":"2018","journal-title":"Clin Res Hepatol Gastroenterol"},{"issue":"02","key":"ref90","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/MOG.0000000000000610","article-title":"Genetically engineered animal models of biliary tract cancers","volume":"36","author":"S Pirenne","year":"2020","journal-title":"Curr Opin Gastroenterol"},{"issue":"07","key":"ref91","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/s41575-022-00739-y","article-title":"Criteria for preclinical models of cholangiocarcinoma: scientific and medical relevance","volume":"20","author":"D F Calvisi","year":"2023","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"19","key":"ref92","doi-asserted-by":"crossref","first-page":"E3806","DOI":"10.1073\/pnas.1619416114","article-title":"Biliary epithelial injury-induced regenerative response by IL-33 promotes cholangiocarcinogenesis from peribiliary glands","volume":"114","author":"H Nakagawa","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"04","key":"ref93","doi-asserted-by":"crossref","first-page":"380","DOI":"10.3390\/cells8040380","article-title":"Comparison of the Opn-CreER and Ck19-CreER drivers in bile ducts of normal and injured mouse livers","volume":"8","author":"B Lesaffer","year":"2019","journal-title":"Cells"},{"issue":"09","key":"ref94","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1158\/0008-5472.CAN-21-2176","article-title":"Concurrent activation of KRAS and canonical Wnt signaling induces premalignant lesions that progress to extrahepatic biliary cancer in mice","volume":"82","author":"M Nagao","year":"2022","journal-title":"Cancer Res"},{"issue":"07","key":"ref95","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1172\/JCI27282","article-title":"Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4 and Pten in mice","volume":"116","author":"X Xu","year":"2006","journal-title":"J Clin Invest"},{"issue":"06","key":"ref96","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1158\/0008-5472.CAN-11-3596","article-title":"KRAS (G12D) and p53 mutation cause primary intrahepatic cholangiocarcinoma","volume":"72","author":"M R O'Dell","year":"2012","journal-title":"Cancer Res"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"23899","DOI":"10.1038\/srep23899","article-title":"A novel mouse model of intrahepatic cholangiocarcinoma induced by liver-specific KRAS activation and Pten deletion","volume":"6","author":"T Ikenoue","year":"2016","journal-title":"Sci Rep"},{"issue":"16","key":"ref98","doi-asserted-by":"crossref","first-page":"4445","DOI":"10.1158\/0008-5472.CAN-17-1123","article-title":"KRAS and Tp53 mutations cause cholangiocyte- and hepatocyte-derived cholangiocarcinoma","volume":"78","author":"M A Hill","year":"2018","journal-title":"Cancer Res"},{"key":"ref99","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.canlet.2018.02.017","article-title":"Combination of KRAS activation and PTEN deletion contributes to murine hepatopancreatic ductal malignancy","volume":"421","author":"Y K Lin","year":"2018","journal-title":"Cancer Lett"},{"issue":"03","key":"ref100","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1002\/hep.31834","article-title":"A novel mouse model of cholangiocarcinoma uncovers a role for Tensin-4 in tumor progression","volume":"74","author":"M Di-Luoffo","year":"2021","journal-title":"Hepatology"},{"issue":"04","key":"ref101","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/path.6139","article-title":"Simultaneous activation of KRAS-Akt and Notch pathways induces extrahepatic biliary cancer via the mTORC1 pathway","volume":"260","author":"M Namikawa","year":"2023","journal-title":"J Pathol"},{"issue":"08","key":"ref102","doi-asserted-by":"crossref","first-page":"108772","DOI":"10.1016\/j.celrep.2021.108772","article-title":"Inhibition of FGF10-ERK signal activation suppresses intraductal papillary neoplasm of the bile duct and its associated carcinomas","volume":"34","author":"H Tomita","year":"2021","journal-title":"Cell Rep"},{"issue":"02","key":"ref103","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/path.4189","article-title":"PTEN loss and KRAS activation cooperate in murine biliary tract malignancies","volume":"230","author":"V Marsh","year":"2013","journal-title":"J Pathol"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"131","DOI":"10.18632\/oncoscience.368","article-title":"KRASG12D upregulates Notch signaling to induce gallbladder tumorigenesis in mice","volume":"4","author":"W C Chung","year":"2017","journal-title":"Oncoscience"},{"issue":"33","key":"ref105","doi-asserted-by":"crossref","first-page":"14763","DOI":"10.1073\/pnas.1009483107","article-title":"Estrogen-dependent gallbladder carcinogenesis in LXRbeta-\/- female mice","volume":"107","author":"C Gabbi","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"ref106","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1002\/1878-0261.12766","article-title":"Evaluation of the chemopreventive potentials of ezetimibe and aspirin in a novel mouse model of gallbladder preneoplasia","volume":"14","author":"L Rosa","year":"2020","journal-title":"Mol Oncol"},{"issue":"04","key":"ref107","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1093\/carcin\/bgh037","article-title":"Thioacetamide-induced intestinal-type cholangiocarcinoma in rat: an animal model recapitulating the multi-stage progression of human cholangiocarcinoma","volume":"25","author":"C N Yeh","year":"2004","journal-title":"Carcinogenesis"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.stem.2021.04.005","article-title":"Building a consensus on definition and nomenclature of human hepatic, biliary and pancreatic organoids","volume":"28","author":"A Marsee","year":"2021","journal-title":"Cell Stem Cell"},{"issue":"01","key":"ref109","doi-asserted-by":"crossref","first-page":"e678","DOI":"10.1002\/ctm2.678","article-title":"Patient-derived organoids for personalized gallbladder cancer modelling and drug screening","volume":"12","author":"B Yuan","year":"2022","journal-title":"Clin Transl Med"},{"issue":"12","key":"ref110","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1038\/nm.4438","article-title":"Human primary liver cancer-derived organoid cultures for disease modeling and drug screening","volume":"23","author":"L Broutier","year":"2017","journal-title":"Nat Med"},{"issue":"04","key":"ref111","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.celrep.2019.03.088","article-title":"Establishment of patient-derived organoids and drug screening for biliary tract carcinoma","volume":"27","author":"Y Saito","year":"2019","journal-title":"Cell Rep"},{"issue":"16","key":"ref112","doi-asserted-by":"crossref","first-page":"8675","DOI":"10.3390\/ijms22168675","article-title":"Patient-derived organoids of cholangiocarcinoma","volume":"22","author":"C F Maier","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"06","key":"ref113","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.stem.2016.04.003","article-title":"A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis","volume":"18","author":"M Fujii","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref114","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cell.2014.11.050","article-title":"Long-term culture of genome-stable bipotent stem cells from adult human liver","volume":"160","author":"M Huch","year":"2015","journal-title":"Cell"}],"container-title":["Seminars in Liver Disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2207-9834.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T23:40:07Z","timestamp":1702683607000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2207-9834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11]]},"references-count":114,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2023,12,15]]},"published-print":{"date-parts":[[2023,11]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2207-9834","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0272-8087","1098-8971"],"issn-type":[{"value":"0272-8087","type":"print"},{"value":"1098-8971","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,11,9]]},"published":{"date-parts":[[2023,11]]}}}