{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:37:16Z","timestamp":1790753836273,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T00:00:00Z","timestamp":1554940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP101195"],"award-info":[{"award-number":["RP101195"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP120715"],"award-info":[{"award-number":["RP120715"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM08307"],"award-info":[{"award-number":["T32 GM08307"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA12512"],"award-info":[{"award-number":["P30CA12512"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U01HG006485"],"award-info":[{"award-number":["U01HG006485"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pediatric hepatocellular carcinoma (HCC) is a rare liver tumor in children with a poor prognosis. Comprehensive molecular profiling to understand the underlying genomic drivers of this tumor has not been completed, and it is unclear whether nonfibrolamellar pediatric HCC is more genomically similar to hepatoblastoma or adult HCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>To characterize the molecular landscape of these tumors, we analyzed a cohort of 15 pediatric non\u2010FL\u2010HCCs by sequencing a panel of cancer\u2010associated genes and conducting copy\u2010number and gene\u2010expression analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected multiple types of molecular alterations in Wnt signaling genes, including <jats:italic>APC<\/jats:italic> inversion, <jats:italic>AMER1<\/jats:italic> somatic mutation, and most commonly <jats:italic>CTNNB1<\/jats:italic> intragenic deletions. There were multiple alterations to the telomerase pathway via <jats:italic>TERT<\/jats:italic> activation or <jats:italic>ATRX<\/jats:italic> mutation. Therapeutically targetable activating mutations in MAPK\/ERK signaling pathway genes, including <jats:italic>MAPK1<\/jats:italic> and <jats:italic>BRAF<\/jats:italic>, were detected in 20% of tumors. <jats:italic>TP53<\/jats:italic> mutations occurred far less frequently in our pediatric HCC cohort than reported in adult cohorts. Tumors arising in children with underlying liver disease were found to be molecularly distinct from the remainder and lacking detectable oncogenic drivers, as compared with those arising in patients without a history of underlying liver disease; the majority of both types were positive for glypican\u20103, another potential therapeutic target.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study revealed pediatric HCC to be a molecularly heterogeneous group of tumors. Those non\u2010FL\u2010HCC tumors arising in the absence of underlying liver disease harbor genetic alterations affecting multiple cancer pathways, most notably Wnt signaling, and share some characteristics with adult HCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.27745","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T09:43:14Z","timestamp":1555062194000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Characterization of pediatric hepatocellular carcinoma reveals genomic heterogeneity and diverse signaling pathway activation"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0021-1409","authenticated-orcid":false,"given":"Katherine","family":"Haines","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Sarabia","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine  Houston Texas"},{"name":"Texas Children's Cancer Center Texas Children's Hospital  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla R.","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine  Houston Texas"},{"name":"Texas Children's Cancer Center Texas Children's Hospital  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"University of Texas Health Sciences Center at San Antonio Greehey Children's Cancer Research Institute  San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev A.","family":"Vasudevan","sequence":"additional","affiliation":[{"name":"Texas Children's Cancer Center Texas Children's Hospital  Houston Texas"},{"name":"Department of Surgery Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andras A.","family":"Heczey","sequence":"additional","affiliation":[{"name":"Texas Children's Cancer Center Texas Children's Hospital  Houston Texas"},{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angshumoy","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine  Houston Texas"},{"name":"Texas Children's Cancer Center Texas Children's Hospital  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton J.","family":"Finegold","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Williams","family":"Parsons","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"},{"name":"Texas Children's Cancer Center Texas Children's Hospital  Houston Texas"},{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-0936","authenticated-orcid":false,"given":"Sharon E.","family":"Plon","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"},{"name":"Texas Children's Cancer Center Texas Children's Hospital  Houston Texas"},{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"L\u00f3pez\u2010Terrada","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine  Houston Texas"},{"name":"Texas Children's Cancer Center Texas Children's Hospital  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/670728","article-title":"Hepatocellular carcinoma in the pediatric population: a population based clinical outcomes study involving 257 patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973\u20132011)","volume":"2015","author":"Lau CSM","year":"2015","journal-title":"HPB Surg"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50375"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.80"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.046"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3252"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3126"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3547"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28888"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbs017"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.11.002"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-0262"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28638"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-7-21"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3940"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10024-001-0121-3"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0630"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4850"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27872"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2016.025"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.27745","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.27745","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.27745","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.27745","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T18:13:34Z","timestamp":1694369614000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.27745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,11]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["10.1002\/pbc.27745"],"URL":"https:\/\/doi.org\/10.1002\/pbc.27745","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,11]]},"assertion":[{"value":"2018-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e27745"}}