{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:37:11Z","timestamp":1790753831221,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Beckwith\u2010Wiedemann Syndrome (BWS) is the most common human overgrowth disorder caused by structural and epigenetic changes to chromosome 11p15. Patients with BWS are predisposed to developing hepatoblastoma (HB). To better understand the mechanism of HB oncogenesis in this cancer predisposition background, we performed the first multi\u2010dimensional study of HB samples collected from patients diagnosed with BWS. This multi\u2010omic investigation of seven BWS HB and five matched nontumor BWS liver samples from 7 unique patients included examination of whole exome sequences, messenger RNA\/microRNA expression, and methylation levels to elucidate the genomic, transcriptomic, and epigenomic landscape of BWS\u2010associated HB. We compared the transcriptional profiles of the BWS samples, both HB and nontumor, to that of control livers. Genes differentially expressed across BWS tissues were identified as BWS HB predisposition factors; this gene group included cell cycle regulators, chromatin organizers, and WNT, mitogen\u2010activated protein kinase (MAPK), and phosphoinositide 3\u2010kinase (PI3K)\/AKT members. We also compared transcriptional changes associated with non\u2010syndromic HB carrying BWS\u2010like 11p15 alterations compared to those without, as well as to BWS HB. Through this analysis, we identified factors specific to 11p15\u2010altered HB oncogenesis, termed the BWS oncogenesis network. We propose that 11p15 alterations drive HB oncogenesis by initially dysregulating cell\u2010cycle regulators and chromatin organizers, including <jats:italic toggle=\"yes\">histone deacetylase 1<\/jats:italic> (<jats:italic toggle=\"yes\">HDAC1<\/jats:italic>), <jats:italic toggle=\"yes\">ATP\u2010dependent helicase X, and F\u2010Box and WD repeat domain containing 7<\/jats:italic>. Furthermore, we found oncogenic factors such as dickkopf WNT signaling pathway inhibitor 1 and 4, <jats:italic toggle=\"yes\">WNT16, forkhead box O3 (FOXO3)<\/jats:italic>, and <jats:italic toggle=\"yes\">MAPK10<\/jats:italic> are differentially expressed in 11p15\u2010altered HB in both the BWS and non\u2010syndromic backgrounds. These genes warrant further investigation as diagnostic or therapeutic targets.<\/jats:p>","DOI":"10.1002\/hep4.1972","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T18:34:46Z","timestamp":1651689286000},"page":"2132-2146","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":18,"title":["Molecular networks of hepatoblastoma predisposition and oncogenesis in Beckwith\u2010Wiedemann syndrome"],"prefix":"10.1097","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7086-9911","authenticated-orcid":false,"given":"Natali S.","family":"Sobel Naveh","sequence":"first","affiliation":[{"name":"Division of Human Genetics and Center for Childhood Cancer Research,Children\u2019s Hospital of Philadelphia,Philadelphia,Pennsylvania,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Traxler","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and Center for Childhood Cancer Research,Children\u2019s Hospital of Philadelphia,Philadelphia,Pennsylvania,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Duffy","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and Center for Childhood Cancer Research,Children\u2019s Hospital of Philadelphia,Philadelphia,Pennsylvania,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1500-9713","authenticated-orcid":false,"given":"Jennifer\u00a0M.","family":"Kalish","sequence":"additional","affiliation":[{"name":"Division of Human Genetics and Center for Childhood Cancer Research,Children\u2019s Hospital of Philadelphia,Philadelphia,Pennsylvania,USA"},{"name":"Departments of Pediatrics and Genetics,Perelman School of Medicine at the University of Pennsylvania,Philadelphia,Pennsylvania,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,5,4]]},"reference":[{"key":"hep41972-bib-0001-20241129","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1002\/cncr.11585","article-title":"Where do we stand with hepatoblastoma? 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