{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:38:28Z","timestamp":1778600308972,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T00:00:00Z","timestamp":1637452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08 CA193915"],"award-info":[{"award-number":["K08 CA193915"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001445","name":"Alex's Lemonade Stand Foundation","doi-asserted-by":"publisher","award":["Epidemiology Grant"],"award-info":[{"award-number":["Epidemiology Grant"]}],"id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001021","name":"Damon Runyon Cancer Research Foundation","doi-asserted-by":"publisher","award":["Clinical Investigator Award"],"award-info":[{"award-number":["Clinical Investigator Award"]}],"id":[{"id":"10.13039\/100001021","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lorenzo \u201cTurtle\u201d Sartini Jr Endowed Chair in Beckwith-Wiedemann Syndrome Research","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"the Victoria Fertitta Fund through the Lorenzo \u201cTurtle\u201d Sartini Jr Endowed Chair in Beck-with-Wiedemann Syndrome Research","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Beckwith\u2013Wiedemann Spectrum (BWSp) is the most common epigenetic childhood cancer predisposition disorder. BWSp is caused by (epi)genetic changes affecting the BWS critical region on chromosome 11p15. Clinically, BWSp represents complex molecular and phenotypic heterogeneity resulting in a range of presentations from Classic BWS to milder features. The previously reported tumor risk based on Classic BWS cohorts is 8\u201310% and routine tumor screening has been recommended. This work investigated the tumor risk and correlation with phenotype within a cohort of patients from Classic BWS to BWSp using a mixed-methods approach to explore phenotype and epigenotype profiles associated with tumor development through statistical analyses with post-hoc retrospective case series review. We demonstrated that tumor risk across BWSp differs from Classic BWS and that certain phenotypic features are associated with specific epigenetic causes; nephromegaly and\/or hyperinsulinism appear associated with cancer in some patients. We also demonstrated that prenatal and perinatal factors that are not currently part of the BWSp classification may factor into tumor risk. Additionally, blood testing results are not necessarily synonymous with tissue testing results. Together, it appears that the current understanding from Classic BWS of (epi)genetics and phenotype correlations with tumors is not represented in the BWSp. Further study is needed in this complex population.<\/jats:p>","DOI":"10.3390\/genes12111839","type":"journal-article","created":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T20:58:21Z","timestamp":1637528301000},"page":"1839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith\u2013Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population"],"prefix":"10.3390","volume":"12","author":[{"given":"Kelly A.","family":"Duffy","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly D.","family":"Getz","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology, Perelman School of Medicine, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan R.","family":"Hathaway","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mallory E.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne P.","family":"MacFarland","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Perelman School of Medicine, Philadelphia, PA 19104, USA"},{"name":"Division of Oncology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1500-9713","authenticated-orcid":false,"given":"Jennifer M.","family":"Kalish","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine, Philadelphia, PA 19104, USA"},{"name":"Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Genetics, Perelman School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nrendo.2017.166","article-title":"Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: An international consensus statement","volume":"14","author":"Brioude","year":"2018","journal-title":"Nat. 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