{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:50:08Z","timestamp":1793116208633,"version":"4.5.0"},"reference-count":176,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100001384","name":"Samuel Waxman Cancer Research Foundation","doi-asserted-by":"publisher","award":["SAF2013-41027"],"award-info":[{"award-number":["SAF2013-41027"]}],"id":[{"id":"10.13039\/100001384","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011475","name":"Cholangiocarcinoma Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011475","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA 020709"],"award-info":[{"award-number":["AA 020709"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DKR0156621"],"award-info":[{"award-number":["DKR0156621"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA165979"],"award-info":[{"award-number":["P30CA165979"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["CA150272P3"],"award-info":[{"award-number":["CA150272P3"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","gastrojournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Gastroenterology"],"published-print":{"date-parts":[[2017,3]]},"DOI":"10.1053\/j.gastro.2016.11.048","type":"journal-article","created":{"date-parts":[[2016,12,30]],"date-time":"2016-12-30T03:18:12Z","timestamp":1483067892000},"page":"745-761","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1024,"title":["Liver Cancer Cell of Origin, Molecular Class, and Effects on\u00a0Patient Prognosis"],"prefix":"10.1053","volume":"152","author":[{"given":"Daniela","family":"Sia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Villanueva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"Friedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep M.","family":"Llovet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1053\/j.gastro.2016.11.048_bib1","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1016\/S0140-6736(12)61689-4","article-title":"Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Murray","year":"2012","journal-title":"Lancet"},{"key":"10.1053\/j.gastro.2016.11.048_bib2","doi-asserted-by":"crossref","first-page":"16018","DOI":"10.1038\/nrdp.2016.18","article-title":"Hepatocellular carcinoma","volume":"2","author":"Llovet","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"10.1053\/j.gastro.2016.11.048_bib3","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nrclinonc.2015.121","article-title":"Advances in targeted therapies for hepatocellular carcinoma in the genomic era","volume":"12","author":"Llovet","year":"2015","journal-title":"Nat Rev Clin Oncol"},{"key":"10.1053\/j.gastro.2016.11.048_bib4","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","article-title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Lozano","year":"2012","journal-title":"Lancet"},{"key":"10.1053\/j.gastro.2016.11.048_bib5","series-title":"WHO classification of tumours of the digestive system","author":"World Health Organization","year":"2010"},{"key":"10.1053\/j.gastro.2016.11.048_bib6","first-page":"87","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J Clin"},{"key":"10.1053\/j.gastro.2016.11.048_bib7","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1016\/j.cgh.2015.08.014","article-title":"Hepatocellular carcinoma from epidemiology to prevention: translating knowledge into practice","volume":"13","author":"Singal","year":"2015","journal-title":"Clin Gastroenterol Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib8","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nrgastro.2016.140","article-title":"Effect of HCV clearance with direct-acting antiviral agents on HCC","volume":"13","author":"Llovet","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib9","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jhep.2016.04.008","article-title":"Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy","volume":"65","author":"Reig","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib10","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jhep.2016.06.015","article-title":"Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals","volume":"65","author":"Conti","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib11","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.jhep.2016.06.019","article-title":"Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis","volume":"65","author":"Cheung","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.canlet.2008.10.040","article-title":"Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection","volume":"286","author":"Chuang","year":"2009","journal-title":"Cancer Lett"},{"key":"10.1053\/j.gastro.2016.11.048_bib13","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1016\/j.jhep.2014.01.021","article-title":"Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma","volume":"60","author":"Bridgewater","year":"2014","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib14","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1158\/1078-0432.CCR-14-3296","article-title":"Molecular pathogenesis and targeted therapies for intrahepatic cholangiocarcinoma","volume":"22","author":"Moeini","year":"2016","journal-title":"Clin Cancer Res"},{"key":"10.1053\/j.gastro.2016.11.048_bib15","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jhep.2012.02.022","article-title":"Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma","volume":"57","author":"Palmer","year":"2012","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1146\/annurev-physiol-021113-170255","article-title":"Cellular homeostasis and repair in the mammalian liver","volume":"77","author":"Stanger","year":"2015","journal-title":"Annu Rev Physiol"},{"key":"10.1053\/j.gastro.2016.11.048_bib17","doi-asserted-by":"crossref","first-page":"13409","DOI":"10.1073\/pnas.1415287111","article-title":"Single cell sequencing reveals low levels of aneuploidy across mammalian tissues","volume":"111","author":"Knouse","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/j.gastro.2016.11.048_bib18","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1055\/s-2004-815564","article-title":"Progenitor cells in diseased human liver","volume":"23","author":"Roskams","year":"2003","journal-title":"Semin Liver Dis"},{"key":"10.1053\/j.gastro.2016.11.048_bib19","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/nm1377","article-title":"A\u00a0novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells","volume":"12","author":"Lee","year":"2006","journal-title":"Nat Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib20","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1002\/ijc.25519","article-title":"CD133 and ALDH may be the molecular markers of cholangiocarcinoma stem cells","volume":"128","author":"Wang","year":"2011","journal-title":"Int J Cancer"},{"key":"10.1053\/j.gastro.2016.11.048_bib21","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.1038\/sj.onc.1209558","article-title":"Liver stem cells and their implication in hepatocellular and cholangiocarcinoma","volume":"25","author":"Roskams","year":"2006","journal-title":"Oncogene"},{"key":"10.1053\/j.gastro.2016.11.048_bib22","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1007\/s10620-013-2585-1","article-title":"Combined hepatocellular cholangiocarcinoma: a case report and review of literature","volume":"58","author":"Singh","year":"2013","journal-title":"Dig Dis Sci"},{"key":"10.1053\/j.gastro.2016.11.048_bib23","first-page":"5239","article-title":"Hepatic biliary epithelial cells acquire epithelial integrity but lose plasticity to differentiate into hepatocytes in\u00a0vitro during development","volume":"126","author":"Tanimizu","year":"2013","journal-title":"J\u00a0Cell Sci"},{"key":"10.1053\/j.gastro.2016.11.048_bib24","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/hep.24712","article-title":"Mature hepatocytes exhibit unexpected plasticity by direct dedifferentiation into liver progenitor cells in culture","volume":"55","author":"Chen","year":"2012","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib25","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.stem.2014.09.008","article-title":"Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes","volume":"15","author":"Tarlow","year":"2014","journal-title":"Cell Stem Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib26","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1158\/0008-5472.CAN-13-1911","article-title":"Cell lineage tracing reveals a biliary origin of intrahepatic cholangiocarcinoma","volume":"74","author":"Guest","year":"2014","journal-title":"Cancer Res"},{"key":"10.1053\/j.gastro.2016.11.048_bib27","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/cr.2012.13","article-title":"Understanding cancer stem cell heterogeneity and plasticity","volume":"22","author":"Tang","year":"2012","journal-title":"Cell Res"},{"key":"10.1053\/j.gastro.2016.11.048_bib28","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/nrc1232","article-title":"Applying the principles of stem-cell biology to cancer","volume":"3","author":"Pardal","year":"2003","journal-title":"Nat Rev Cancer"},{"key":"10.1053\/j.gastro.2016.11.048_bib29","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nrc3217","article-title":"Epithelial stem cells, wound healing and cancer","volume":"12","author":"Arwert","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"10.1053\/j.gastro.2016.11.048_bib30","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/nature07602","article-title":"Crypt stem cells as the cells-of-origin of intestinal cancer","volume":"457","author":"Barker","year":"2009","journal-title":"Nature"},{"key":"10.1053\/j.gastro.2016.11.048_bib31","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nature07589","article-title":"Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation","volume":"457","author":"Zhu","year":"2009","journal-title":"Nature"},{"key":"10.1053\/j.gastro.2016.11.048_bib32","doi-asserted-by":"crossref","first-page":"7431","DOI":"10.1073\/pnas.1012720108","article-title":"Identifying the cellular origin of squamous skin tumors","volume":"108","author":"Lapouge","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/j.gastro.2016.11.048_bib33","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1053\/j.gastro.2009.05.044","article-title":"Stem cells and liver regeneration","volume":"137","author":"Duncan","year":"2009","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib34","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0925-4773(02)00338-6","article-title":"The role of hepatocytes and oval cells in liver regeneration and repopulation","volume":"120","author":"Fausto","year":"2003","journal-title":"Mech Dev"},{"key":"10.1053\/j.gastro.2016.11.048_bib35","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.stem.2014.04.010","article-title":"Stem\/progenitor cells in liver development, homeostasis, regeneration, and reprogramming","volume":"14","author":"Miyajima","year":"2014","journal-title":"Cell Stem Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib36","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1002\/hep.20214","article-title":"Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells","volume":"39","author":"Fausto","year":"2004","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib37","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1002\/hep.20130","article-title":"Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers","volume":"39","author":"Roskams","year":"2004","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib38","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/j.1365-2559.2010.03668.x","article-title":"Immunohistochemical classification of ductular reactions in human liver","volume":"57","author":"Turanyi","year":"2010","journal-title":"Histopathology"},{"key":"10.1053\/j.gastro.2016.11.048_bib39","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s12015-010-9188-4","article-title":"Liver stem\/progenitor cells in the canals of Hering: cellular origin of hepatocellular carcinoma with bile duct tumor thrombi?","volume":"6","author":"Peng","year":"2010","journal-title":"Stem Cell Rev"},{"key":"10.1053\/j.gastro.2016.11.048_bib40","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/ncb3203","article-title":"Hepatic progenitor cells of biliary origin with liver repopulation capacity","volume":"17","author":"Lu","year":"2015","journal-title":"Nat Cell Biol"},{"key":"10.1053\/j.gastro.2016.11.048_bib41","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/ng.722","article-title":"Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine","volume":"43","author":"Furuyama","year":"2011","journal-title":"Nat Genet"},{"key":"10.1053\/j.gastro.2016.11.048_bib42","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1053\/j.gastro.2012.08.024","article-title":"Liver progenitor cells yield functional hepatocytes in response to chronic liver injury in mice","volume":"143","author":"Espanol-Suner","year":"2012","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib43","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1053\/jhep.2003.50104","article-title":"Mouse A6-positive hepatic oval cells also express several hematopoietic stem cell markers","volume":"37","author":"Petersen","year":"2003","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib44","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.stem.2014.06.003","article-title":"Adult hepatocytes are generated by self-duplication rather than stem cell differentiation","volume":"15","author":"Yanger","year":"2014","journal-title":"Cell Stem Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib45","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.celrep.2014.07.003","article-title":"Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury","volume":"8","author":"Schaub","year":"2014","journal-title":"Cell Rep"},{"key":"10.1053\/j.gastro.2016.11.048_bib46","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/nature14863","article-title":"Self-renewing diploid Axin2(+) cells fuel homeostatic renewal of the liver","volume":"524","author":"Wang","year":"2015","journal-title":"Nature"},{"key":"10.1053\/j.gastro.2016.11.048_bib47","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1242\/dev.016634","article-title":"Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression","volume":"135","author":"Suzuki","year":"2008","journal-title":"Development"},{"key":"10.1053\/j.gastro.2016.11.048_bib48","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.cell.2015.07.026","article-title":"Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer","volume":"162","author":"Font-Burgada","year":"2015","journal-title":"Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib49","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nature15201","article-title":"Regenerative biology: maintaining liver mass","volume":"524","author":"Zaret","year":"2015","journal-title":"Nature"},{"key":"10.1053\/j.gastro.2016.11.048_bib50","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1101\/gad.214601.113","article-title":"Specific fate decisions in adult hepatic progenitor cells driven by MET and EGFR signaling","volume":"27","author":"Kitade","year":"2013","journal-title":"Genes Dev"},{"key":"10.1053\/j.gastro.2016.11.048_bib51","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1053\/j.gastro.2007.06.016","article-title":"Enhanced self-renewal capability in hepatic stem\/progenitor cells drives cancer initiation","volume":"133","author":"Chiba","year":"2007","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib52","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.cell.2014.05.051","article-title":"p53-dependent Nestin regulation links tumor suppression to cellular plasticity in liver cancer","volume":"158","author":"Tschaharganeh","year":"2014","journal-title":"Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib53","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2015.02.027","article-title":"YAP inhibition restores hepatocyte differentiation in advanced HCC, leading to tumor regression","author":"Fitamant","year":"2015","journal-title":"Cell Rep"},{"key":"10.1053\/j.gastro.2016.11.048_bib54","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1073\/pnas.0911427107","article-title":"Hippo signaling is a potent in\u00a0vivo growth and tumor suppressor pathway in the mammalian liver","volume":"107","author":"Lu","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/j.gastro.2016.11.048_bib55","doi-asserted-by":"crossref","first-page":"8248","DOI":"10.1073\/pnas.0912203107","article-title":"The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis","volume":"107","author":"Lee","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/j.gastro.2016.11.048_bib56","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1101\/gad.1938710","article-title":"Nf2\/Merlin controls progenitor homeostasis and tumorigenesis in the liver","volume":"24","author":"Benhamouche","year":"2010","journal-title":"Genes Dev"},{"key":"10.1053\/j.gastro.2016.11.048_bib57","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1053\/j.gastro.2013.03.013","article-title":"Modeling pathogenesis of primary liver cancer in lineage-specific mouse cell types","volume":"145","author":"Holczbauer","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib58","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrgastro.2012.23","article-title":"The biliary tree\u2014a reservoir of multipotent stem cells","volume":"9","author":"Cardinale","year":"2012","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib59","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1002\/hep.24590","article-title":"Multipotent stem\/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes, and pancreatic islets","volume":"54","author":"Cardinale","year":"2011","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib60","first-page":"743790","article-title":"Fibrolamellar carcinoma: 2012 update","volume":"2012","author":"Torbenson","year":"2012","journal-title":"Scientifica (Cairo)"},{"key":"10.1053\/j.gastro.2016.11.048_bib61","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1053\/j.gastro.2012.09.002","article-title":"Notch signaling is activated in human hepatocellular carcinoma and induces tumor formation in mice","volume":"143","author":"Villanueva","year":"2012","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib62","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.ccr.2013.04.019","article-title":"A\u00a0critical role for notch signaling in the formation of cholangiocellular carcinomas","volume":"23","author":"Zender","year":"2013","journal-title":"Cancer Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib63","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nature13441","article-title":"Mutant IDH inhibits HNF-4alpha to block hepatocyte differentiation and promote biliary cancer","volume":"513","author":"Saha","year":"2014","journal-title":"Nature"},{"key":"10.1053\/j.gastro.2016.11.048_bib64","doi-asserted-by":"crossref","first-page":"23899","DOI":"10.1038\/srep23899","article-title":"A\u00a0novel mouse model of intrahepatic cholangiocarcinoma induced by liver-specific Kras activation and Pten deletion","volume":"6","author":"Ikenoue","year":"2016","journal-title":"Sci Rep"},{"key":"10.1053\/j.gastro.2016.11.048_bib65","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1172\/JCI77995","article-title":"Hepatocellular carcinoma originates from hepatocytes and not from the progenitor\/biliary compartment","volume":"125","author":"Mu","year":"2015","journal-title":"J\u00a0Clin Invest"},{"key":"10.1053\/j.gastro.2016.11.048_bib66","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1002\/hep.28602","article-title":"Genetic lineage tracing analysis of the cell of origin of hepatotoxin-induced liver tumors in mice","volume":"64","author":"Shin","year":"2016","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib67","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1172\/JCI78585","article-title":"Lineage fate of ductular reactions in liver injury and carcinogenesis","volume":"125","author":"Jors","year":"2015","journal-title":"J\u00a0Clin Invest"},{"key":"10.1053\/j.gastro.2016.11.048_bib68","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.cell.2013.09.031","article-title":"Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling","volume":"155","author":"He","year":"2013","journal-title":"Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib69","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/hep.28671","article-title":"Deconvolution of the cellular origin in hepatocellular carcinoma: Hepatocytes take the center stage","volume":"64","author":"Marquardt","year":"2016","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib70","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.ccell.2016.04.006","article-title":"p62, upregulated during preneoplasia, induces hepatocellular carcinogenesis by maintaining survival of stressed HCC-initiating cells","volume":"29","author":"Umemura","year":"2016","journal-title":"Cancer Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib71","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1101\/gad.207803.112","article-title":"Robust cellular reprogramming occurs spontaneously during liver regeneration","volume":"27","author":"Yanger","year":"2013","journal-title":"Genes Dev"},{"key":"10.1053\/j.gastro.2016.11.048_bib72","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1172\/JCI63065","article-title":"Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes","volume":"122","author":"Sekiya","year":"2012","journal-title":"J\u00a0Clin Invest"},{"key":"10.1053\/j.gastro.2016.11.048_bib73","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1172\/JCI63212","article-title":"Cholangiocarcinomas can originate from hepatocytes in mice","volume":"122","author":"Fan","year":"2012","journal-title":"J\u00a0Clin Invest"},{"key":"10.1053\/j.gastro.2016.11.048_bib74","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1002\/hep.22238","article-title":"Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin","volume":"47","author":"Komuta","year":"2008","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib75","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1053\/j.gastro.2013.01.002","article-title":"Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma","volume":"144","author":"Hernandez-Gea","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib76","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib77","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1002\/hep.28487","article-title":"Oncogenic driver genes and the inflammatory microenvironment dictate liver tumor phenotype","volume":"63","author":"Matter","year":"2016","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib78","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/ni.3290","article-title":"Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma","volume":"16","author":"Finkin","year":"2015","journal-title":"Nat Immunol"},{"key":"10.1053\/j.gastro.2016.11.048_bib79","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1097\/CCO.0000000000000042","article-title":"Contributions of metabolic dysregulation and inflammation to nonalcoholic steatohepatitis, hepatic fibrosis, and cancer","volume":"26","author":"Lade","year":"2014","journal-title":"Curr Opin Oncol"},{"key":"10.1053\/j.gastro.2016.11.048_bib80","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.ccell.2014.09.003","article-title":"Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes nonalcoholic steatohepatitis and liver cancer via cross-talk with hepatocytes","volume":"26","author":"Wolf","year":"2014","journal-title":"Cancer Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib81","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nature16969","article-title":"NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis","volume":"531","author":"Ma","year":"2016","journal-title":"Nature"},{"key":"10.1053\/j.gastro.2016.11.048_bib82","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1002\/hep.27687","article-title":"IL-33 facilitates oncogene-induced cholangiocarcinoma in mice by an interleukin-6-sensitive mechanism","volume":"61","author":"Yamada","year":"2015","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib83","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1053\/j.gastro.2013.10.013","article-title":"Pathogenesis, diagnosis, and management of cholangiocarcinoma","volume":"145","author":"Rizvi","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib84","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1002\/hep.20966","article-title":"Interleukin 6 upregulates myeloid cell leukemia-1 expression through a STAT3 pathway in cholangiocarcinoma cells","volume":"42","author":"Isomoto","year":"2005","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib85","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1053\/j.gastro.2013.01.001","article-title":"Integrative molecular analysis of intrahepatic cholangiocarcinoma reveals 2 classes that have different outcomes","volume":"144","author":"Sia","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib86","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/nm.3944","article-title":"Natural and therapy-induced immunosurveillance in breast cancer","volume":"21","author":"Kroemer","year":"2015","journal-title":"Nat Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib87","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/nrgastro.2015.173","article-title":"Immunological landscape and immunotherapy of hepatocellular carcinoma","volume":"12","author":"Prieto","year":"2015","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib88","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1136\/gutjnl-2014-307990","article-title":"Current concepts of immune based treatments for patients with HCC: from basic science to novel treatment approaches","volume":"64","author":"Greten","year":"2015","journal-title":"Gut"},{"issue":"suppl","key":"10.1053\/j.gastro.2016.11.048_bib89","article-title":"Phase\u00a0I\/II\u00a0safety and antitumor activity of nivolumab in\u00a0patients with advanced hepatocellular carcinoma (HCC): CA209-040 (abstr LBA101)","volume":"33","author":"El-Khoueiry","year":"2015","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1053\/j.gastro.2016.11.048_bib90","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1007\/s00262-011-1172-6","article-title":"An immune-active tumor microenvironment favors clinical response to ipilimumab","volume":"61","author":"Ji","year":"2012","journal-title":"Cancer Immunol Immunother"},{"key":"10.1053\/j.gastro.2016.11.048_bib91","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1158\/2159-8290.CD-13-0458","article-title":"Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation","volume":"4","author":"Bald","year":"2014","journal-title":"Cancer Discov"},{"key":"10.1053\/j.gastro.2016.11.048_bib92","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1056\/NEJMoa1406498","article-title":"Genetic basis for clinical response to CTLA-4 blockade in melanoma","volume":"371","author":"Snyder","year":"2014","journal-title":"N\u00a0Engl J Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib93","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1200\/JCO.2014.59.4358","article-title":"Immune checkpoint blockade in cancer therapy","volume":"33","author":"Postow","year":"2015","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1053\/j.gastro.2016.11.048_bib94","unstructured":"Sia D, Jiao Y, Martinez-Quetglas I, et\u00a0al. Characterization of the immune class of hepatocellular carcinoma (abstr\u00a0O-007). 10th ILCA Annual Conference; September 9-11, 2016; Vancouver, Canada."},{"key":"10.1053\/j.gastro.2016.11.048_bib95","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/ng.3375","article-title":"Genomic spectra of biliary tract cancer","volume":"47","author":"Nakamura","year":"2015","journal-title":"Nat Genet"},{"key":"10.1053\/j.gastro.2016.11.048_bib96","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jhep.2016.05.035","article-title":"Genetic profiling of hepatocellular carcinoma using next-generation sequencing","volume":"65","author":"Schulze","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib97","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1053\/j.gastro.2015.05.061","article-title":"Genetic landscape and biomarkers of hepatocellular carcinoma","volume":"149","author":"Zucman-Rossi","year":"2015","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib98","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1053\/j.gastro.2016.09.001","article-title":"IGF2 Is up-regulated by epigenetic mechanisms in hepatocellular carcinomas and is an actionable oncogene product in experimental models","volume":"151","author":"Martinez-Quetglas","year":"2016","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib99","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1053\/j.gastro.2011.02.006","article-title":"Combining clinical, pathology, and gene expression data to predict\u00a0recurrence of hepatocellular carcinoma","volume":"140","author":"Villanueva","year":"2011","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib100","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1053\/j.gastro.2013.03.051","article-title":"A\u00a0hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection","volume":"145","author":"Nault","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib101","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1053\/j.gastro.2011.02.009","article-title":"MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a","volume":"140","author":"Toffanin","year":"2011","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib102","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1002\/hep.27732","article-title":"DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma","volume":"61","author":"Villanueva","year":"2015","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib103","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1056\/NEJMoa0804525","article-title":"Gene expression in fixed tissues and outcome in hepatocellular carcinoma","volume":"359","author":"Hoshida","year":"2008","journal-title":"N\u00a0Engl J Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib104","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1002\/hep.26898","article-title":"Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma","volume":"59","author":"Fuchs","year":"2014","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib105","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"10.1053\/j.gastro.2016.11.048_bib106","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/ng.3252","article-title":"Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets","volume":"47","author":"Schulze","year":"2015","journal-title":"Nat Genet"},{"key":"10.1053\/j.gastro.2016.11.048_bib107","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/ng.3126","article-title":"Trans-ancestry mutational landscape of hepatocellular carcinoma genomes","volume":"46","author":"Totoki","year":"2014","journal-title":"Nat Genet"},{"key":"10.1053\/j.gastro.2016.11.048_bib108","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/ng.3547","article-title":"Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer","volume":"48","author":"Fujimoto","year":"2016","journal-title":"Nat Genet"},{"key":"10.1053\/j.gastro.2016.11.048_bib109","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/ng.2295","article-title":"Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma","volume":"44","author":"Sung","year":"2012","journal-title":"Nat Genet"},{"key":"10.1053\/j.gastro.2016.11.048_bib110","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/ng.3389","article-title":"Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas","volume":"47","author":"Nault","year":"2015","journal-title":"Nat Genet"},{"key":"10.1053\/j.gastro.2016.11.048_bib111","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1056\/NEJMoa1214886","article-title":"Crizotinib versus chemotherapy in advanced ALK-positive lung cancer","volume":"368","author":"Shaw","year":"2013","journal-title":"N\u00a0Engl J Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib112","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1158\/2159-8290.CD-14-1029","article-title":"First selective small molecule inhibitor of fgfr4 for the treatment of hepatocellular carcinomas with an activated FGFR4 signaling pathway","volume":"5","author":"Hagel","year":"2015","journal-title":"Cancer Discov"},{"key":"10.1053\/j.gastro.2016.11.048_bib113","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1158\/1535-7163.MCT-14-0768","article-title":"Loss of tuberous sclerosis complex 2 (TSC2) is frequent in hepatocellular carcinoma and predicts response to mTORC1 inhibitor everolimus","volume":"14","author":"Huynh","year":"2015","journal-title":"Mol Cancer Ther"},{"key":"10.1053\/j.gastro.2016.11.048_bib114","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.jhep.2016.04.015","article-title":"Integrative biomarker analyses indicate etiological variations in hepatocellular carcinoma","volume":"65","author":"Zhu","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib115","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N\u00a0Engl J Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib116","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0140-6736(16)32453-9","article-title":"Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"389","author":"Bruix","year":"2017","journal-title":"Lancet"},{"key":"10.1053\/j.gastro.2016.11.048_bib117","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ccr.2011.01.040","article-title":"Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by oncogenomic screening","volume":"19","author":"Sawey","year":"2011","journal-title":"Cancer Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib118","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1245\/s10434-010-0985-4","article-title":"The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM","volume":"17","author":"Edge","year":"2010","journal-title":"Ann Surg Oncol"},{"key":"10.1053\/j.gastro.2016.11.048_bib119","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1002\/hep.25890","article-title":"Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma","volume":"56","author":"Oishi","year":"2012","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib120","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/hep.21467","article-title":"Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets","volume":"45","author":"Boyault","year":"2007","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib121","doi-asserted-by":"crossref","first-page":"7385","DOI":"10.1158\/0008-5472.CAN-09-1089","article-title":"Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma","volume":"69","author":"Hoshida","year":"2009","journal-title":"Cancer Res"},{"key":"10.1053\/j.gastro.2016.11.048_bib122","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1158\/0008-5472.CAN-09-2823","article-title":"Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma","volume":"70","author":"Woo","year":"2010","journal-title":"Cancer Res"},{"key":"10.1053\/j.gastro.2016.11.048_bib123","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1053\/j.gastro.2013.02.018","article-title":"Genomic decoding of intrahepatic cholangiocarcinoma reveals therapeutic opportunities","volume":"144","author":"Andersen","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib124","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1038\/ng.2806","article-title":"Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers","volume":"45","author":"Chan-On","year":"2013","journal-title":"Nat Genet"},{"key":"10.1053\/j.gastro.2016.11.048_bib125","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1038\/ng.2813","article-title":"Exome sequencing\u00a0identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas","volume":"45","author":"Jiao","year":"2013","journal-title":"Nat Genet"},{"key":"10.1053\/j.gastro.2016.11.048_bib126","doi-asserted-by":"crossref","first-page":"6087","DOI":"10.1038\/ncomms7087","article-title":"Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma","volume":"6","author":"Sia","year":"2015","journal-title":"Nat Commun"},{"key":"10.1053\/j.gastro.2016.11.048_bib127","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1634\/theoncologist.2013-0352","article-title":"New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing","volume":"19","author":"Ross","year":"2014","journal-title":"Oncologist"},{"key":"10.1053\/j.gastro.2016.11.048_bib128","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.18632\/oncotarget.1943","article-title":"Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups","volume":"5","author":"Simbolo","year":"2014","journal-title":"Oncotarget"},{"key":"10.1053\/j.gastro.2016.11.048_bib129","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.1038\/ncomms7120","article-title":"Whole-genome mutational landscape of liver cancers displaying biliary phenotype reveals hepatitis impact and molecular diversity","volume":"6","author":"Fujimoto","year":"2015","journal-title":"Nat Commun"},{"key":"10.1053\/j.gastro.2016.11.048_bib130","doi-asserted-by":"crossref","first-page":"5696","DOI":"10.1038\/ncomms6696","article-title":"Mutational landscape of intrahepatic cholangiocarcinoma","volume":"5","author":"Zou","year":"2014","journal-title":"Nat Commun"},{"key":"10.1053\/j.gastro.2016.11.048_bib131","doi-asserted-by":"crossref","first-page":"e115383","DOI":"10.1371\/journal.pone.0115383","article-title":"Mutation profiling in\u00a0cholangiocarcinoma: prognostic and therapeutic implications","volume":"9","author":"Churi","year":"2014","journal-title":"PLoS One"},{"key":"10.1053\/j.gastro.2016.11.048_bib132","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1002\/hep.26890","article-title":"Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma","volume":"59","author":"Arai","year":"2014","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib133","doi-asserted-by":"crossref","first-page":"e1004135","DOI":"10.1371\/journal.pgen.1004135","article-title":"Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma","volume":"10","author":"Borad","year":"2014","journal-title":"PLoS Genet"},{"key":"10.1053\/j.gastro.2016.11.048_bib134","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.humpath.2014.03.014","article-title":"Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma","volume":"45","author":"Graham","year":"2014","journal-title":"Hum Pathol"},{"key":"10.1053\/j.gastro.2016.11.048_bib135","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1158\/2159-8290.CD-13-0050","article-title":"Identification of targetable FGFR gene fusions in diverse cancers","volume":"3","author":"Wu","year":"2013","journal-title":"Cancer Discov"},{"key":"10.1053\/j.gastro.2016.11.048_bib136","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1200\/JCO.2016.67.2048","volume":"35","author":"Nogova","year":"2017","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.gastro.2016.11.048_bib137","unstructured":"Mazzaferro V, Shaib W, Rimassa L, et\u00a0al. ARQ 087, an oral pan-fibroblast growth factor receptor (FGFR) inhibitor, in patients with advanced and\/or metastatic intrahepatic cholangiocarcinoma (iCCA). https:\/\/globenewswire.com\/news-release\/2016\/06\/30\/852679\/0\/en\/ArQule-Presents-Preliminary-Clinical-Data-for-ARQ-087-Demonstrating-Evidence-of-Anticancer-Activity-in-Intrahepatic-Cholangiocarcinoma-at-the-ESMO-18th-World-Congress-on-Gastrointe.html\u00a02016."},{"key":"10.1053\/j.gastro.2016.11.048_bib138","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1053\/j.gastro.2014.12.028","article-title":"Unique genomic\u00a0profile of fibrolamellar hepatocellular carcinoma","volume":"148","author":"Cornella","year":"2015","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib139","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1126\/science.1249484","article-title":"Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma","volume":"343","author":"Honeyman","year":"2014","journal-title":"Science"},{"key":"10.1053\/j.gastro.2016.11.048_bib140","doi-asserted-by":"crossref","first-page":"E5916","DOI":"10.1073\/pnas.1424894112","article-title":"Transcriptomic characterization of fibrolamellar hepatocellular carcinoma","volume":"112","author":"Simon","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/j.gastro.2016.11.048_bib141","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ccr.2008.11.002","article-title":"Hepatic stem-like phenotype and interplay of Wnt\/beta-catenin and Myc signaling in aggressive childhood liver cancer","volume":"14","author":"Cairo","year":"2008","journal-title":"Cancer Cell"},{"key":"10.1053\/j.gastro.2016.11.048_bib142","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/hep.28621","article-title":"Patient-derived xenografts from pediatric liver cancer predict tumor recurrence and advise clinical management","volume":"64","author":"Nicolle","year":"2016","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib143","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jhep.2016.04.009","article-title":"Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer","volume":"65","author":"Bissig-Choisat","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib144","series-title":"Combined hepatocellular-cholangiocarcinoma. WHO classification of tumours of the digestive system","first-page":"225","author":"Theise","year":"2010"},{"key":"10.1053\/j.gastro.2016.11.048_bib145","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1093\/carcin\/bgs208","article-title":"Combined hepatocellular-cholangiocarcinomas exhibit progenitor features and activation of Wnt and TGFbeta signaling pathways","volume":"33","author":"Coulouarn","year":"2012","journal-title":"Carcinogenesis"},{"key":"10.1053\/j.gastro.2016.11.048_bib146","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhep.2017.01.010","article-title":"Mixed hepatocellular-cholangiocarcinoma tumors: cholangiolocellular carcinoma is a distinct molecular entity","author":"Moeini","year":"2017","journal-title":"J Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib147","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1113205","article-title":"Intratumor heterogeneity and branched evolution revealed by multiregion sequencing","volume":"366","author":"Gerlinger","year":"2012","journal-title":"N\u00a0Engl J Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib148","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/nm.3915","article-title":"Toward understanding and exploiting tumor heterogeneity","volume":"21","author":"Alizadeh","year":"2015","journal-title":"Nat Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib149","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1056\/NEJMoa041588","article-title":"A\u00a0multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer","volume":"351","author":"Paik","year":"2004","journal-title":"N\u00a0Engl J Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib150","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1200\/JCO.2009.21.9170","article-title":"American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy","volume":"27","author":"Allegra","year":"2009","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1053\/j.gastro.2016.11.048_bib151","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.jhep.2011.12.001","article-title":"EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma","volume":"56","year":"2012","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2016.11.048_bib152","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1093\/jnci\/88.20.1456","article-title":"Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers","volume":"88","author":"Hayes","year":"1996","journal-title":"J\u00a0Natl Cancer Inst"},{"key":"10.1053\/j.gastro.2016.11.048_bib153","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1093\/jnci\/dji237","article-title":"Reporting recommendations for tumor marker prognostic studies (REMARK)","volume":"97","author":"McShane","year":"2005","journal-title":"J\u00a0Natl Cancer Inst"},{"key":"10.1053\/j.gastro.2016.11.048_bib154","doi-asserted-by":"crossref","first-page":"e5595","DOI":"10.1136\/bmj.e5595","article-title":"Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes","volume":"346","author":"Hemingway","year":"2013","journal-title":"BMJ"},{"key":"10.1053\/j.gastro.2016.11.048_bib155","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1093\/jnci\/djp335","article-title":"Use of archived specimens in evaluation of prognostic and predictive biomarkers","volume":"101","author":"Simon","year":"2009","journal-title":"J\u00a0Natl Cancer Inst"},{"key":"10.1053\/j.gastro.2016.11.048_bib156","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1056\/NEJMoa1510764","article-title":"prospective validation of a 21-gene expression assay in breast cancer","volume":"373","author":"Sparano","year":"2015","journal-title":"N\u00a0Engl J Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib157","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1158\/1078-0432.CCR-11-2175","article-title":"Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma","volume":"18","author":"Llovet","year":"2012","journal-title":"Clin Cancer Res"},{"key":"10.1053\/j.gastro.2016.11.048_bib158","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1053\/j.gastro.2013.01.021","article-title":"Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis","volume":"144","author":"Hoshida","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2016.11.048_bib159","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1056\/NEJMoa0901282","article-title":"MicroRNA expression, survival, and response to interferon in liver cancer","volume":"361","author":"Ji","year":"2009","journal-title":"N\u00a0Engl J Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib160","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1158\/0008-5472.CAN-07-6013","article-title":"EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma","volume":"68","author":"Yamashita","year":"2008","journal-title":"Cancer Res"},{"key":"10.1053\/j.gastro.2016.11.048_bib161","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/hep.22160","article-title":"Identification of metastasis-related microRNAs in hepatocellular carcinoma","volume":"47","author":"Budhu","year":"2008","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib162","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","article-title":"Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer","volume":"362","author":"Valle","year":"2010","journal-title":"N\u00a0Engl J Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib163","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1136\/jclinpath-2013-201806","article-title":"Epithelial-mesenchymal transition phenotypes are associated with patient survival in intrahepatic cholangiocarcinoma","volume":"67","author":"Gu","year":"2014","journal-title":"J\u00a0Clin Pathol"},{"key":"10.1053\/j.gastro.2016.11.048_bib164","doi-asserted-by":"crossref","first-page":"e96860","DOI":"10.1371\/journal.pone.0096860","article-title":"Comprehensive multiple molecular profile of epithelial mesenchymal transition in intrahepatic cholangiocarcinoma patients","volume":"9","author":"Huang","year":"2014","journal-title":"PLoS One"},{"key":"10.1053\/j.gastro.2016.11.048_bib165","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1002\/hep.26577","article-title":"Molecular profiling of stroma identifies osteopontin as an independent predictor of poor prognosis in intrahepatic cholangiocarcinoma","volume":"58","author":"Sulpice","year":"2013","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib166","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1186\/s12885-015-1270-5","article-title":"A\u00a0microRNA profile associated with Opisthorchis viverrini-induced cholangiocarcinoma in tissue and plasma","volume":"15","author":"Plieskatt","year":"2015","journal-title":"BMC Cancer"},{"key":"10.1053\/j.gastro.2016.11.048_bib167","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/hep.27050","article-title":"Human bile contains microRNA-laden extracellular vesicles that can be used for cholangiocarcinoma diagnosis","volume":"60","author":"Li","year":"2014","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2016.11.048_bib168","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12885-015-1067-6","article-title":"Identification of a novel microRNA signature associated with intrahepatic cholangiocarcinoma (ICC) patient prognosis","volume":"15","author":"Zhang","year":"2015","journal-title":"BMC Cancer"},{"key":"10.1053\/j.gastro.2016.11.048_bib169","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1056\/NEJMra1404198","article-title":"Pancreatic adenocarcinoma","volume":"371","author":"Ryan","year":"2014","journal-title":"N\u00a0Engl J Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib170","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1056\/NEJMc0904160","article-title":"BRAF mutation in metastatic colorectal cancer","volume":"361","author":"Tol","year":"2009","journal-title":"N\u00a0Engl J Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib171","doi-asserted-by":"crossref","first-page":"6063","DOI":"10.1158\/0008-5472.CAN-05-0404","article-title":"Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers","volume":"65","author":"Samowitz","year":"2005","journal-title":"Cancer Res"},{"key":"10.1053\/j.gastro.2016.11.048_bib172","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1245\/s10434-015-5046-6","article-title":"Cholangiocarcinoma heterogeneity revealed by multigene mutational profiling: clinical and prognostic relevance in surgically resected patients","volume":"23","author":"Ruzzenente","year":"2016","journal-title":"Ann Surg Oncol"},{"key":"10.1053\/j.gastro.2016.11.048_bib173","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1038\/onc.2012.315","article-title":"Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas","volume":"32","author":"Wang","year":"2013","journal-title":"Oncogene"},{"key":"10.1053\/j.gastro.2016.11.048_bib174","first-page":"263","article-title":"Liquid biopsy in liver cancer","volume":"19","author":"Labgaa","year":"2015","journal-title":"Discov Med"},{"key":"10.1053\/j.gastro.2016.11.048_bib175","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1053\/j.gastro.2013.11.045","article-title":"Regeneration of liver after extreme hepatocyte loss occurs mainly via biliary transdifferentiation in zebrafish","volume":"146","author":"He","year":"2014","journal-title":"Gastroenterology"},{"issue":"suppl","key":"10.1053\/j.gastro.2016.11.048_bib176","article-title":"A\u00a0randomized, multicenter, phase 3 study of nivolumab vs sorafenib as first-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): CheckMate-459 (abstr TPS4147)","volume":"34","author":"Sangro","year":"2016","journal-title":"J\u00a0Clin Oncol"}],"container-title":["Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0016508516355299?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0016508516355299?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:42:39Z","timestamp":1762162959000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016508516355299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3]]},"references-count":176,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["S0016508516355299"],"URL":"https:\/\/doi.org\/10.1053\/j.gastro.2016.11.048","relation":{},"ISSN":["0016-5085"],"issn-type":[{"value":"0016-5085","type":"print"}],"subject":[],"published":{"date-parts":[[2017,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Liver Cancer Cell of Origin, Molecular Class, and Effects on\u00a0Patient Prognosis","name":"articletitle","label":"Article Title"},{"value":"Gastroenterology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1053\/j.gastro.2016.11.048","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 by the AGA Institute","name":"copyright","label":"Copyright"}]}}