{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:03:57Z","timestamp":1791201837349,"version":"4.2.0"},"reference-count":63,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["IG 2020 ID 24405"],"award-info":[{"award-number":["IG 2020 ID 24405"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Wilms Tumour (WT), the most common kidney cancer in children, presents features of altered kidney development and frequently exhibits molecular alterations at the 11p15.5 imprinted locus, affecting the\n                    <jats:italic>IGF2<\/jats:italic>\n                    and\n                    <jats:italic>H19<\/jats:italic>\n                    genes, which contribute to tumour growth and predisposition. The epigenetic landscape beyond 11p15.5 suggests diagnostic and prognostic potential, but its link to transcriptomic changes is largely unexplored. We integrated methylomic and transcriptomic datasets of 27 primary tumours and matched non\u2010neoplastic kidneys. DNA methylation profiling identified around 9000 differentially methylated CpG sites distinguishing neoplastic from non\u2010neoplastic tissue and other paediatric cancers, thus representing a novel WT\u2010specific epigenetic signature. We found that cases with Imprinting Centre 1 (IC1) gain of methylation exhibited the most extensive epigenetic alterations; cases with 11p15.5 loss of heterozygosity showed intermediate changes, whereas regressive tumours with largely normal 11p15.5 status were less affected. Three methylation clusters corresponding to transcriptomic subtypes were identified, characterised by distinct tumour microenvironment and chemosensitivity predictions: a regressive\u2010enriched, immune\u2010infiltrated group predicted to respond to paclitaxel, a proliferative group sensitive to doxorubicin, and a stromal\u2010like intermediate group. Combined analysis of methylation and expression data revealed more than 900 genes under epigenetic control, which contributed to defining the WT subtypes. Analysis of the\n                    <jats:italic>IGF2<\/jats:italic>\n                    \/\n                    <jats:italic>H19<\/jats:italic>\n                    locus uncovered\u00a0multiple regulatory mechanisms underlying\n                    <jats:italic>IGF2<\/jats:italic>\n                    activation, including imprinting defects at IC1, methylation changes at DMR0, differential promoter usage and transcriptional modulation by PLAG1 and BAHD1. These findings define the epigenetic alterations underlying WT heterogeneity and support improved molecular stratification and therapeutic approaches.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70680","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:41:28Z","timestamp":1785465688000},"page":"2736-2754","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>DNA<\/scp>\n                    Methylation and Transcriptomic Profiles of Wilms Tumour Reveal New Deregulated Genes and Epigenetic Processes Relevant for Tumour Stratification and Management"],"prefix":"10.1002","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9636-2513","authenticated-orcid":false,"given":"Abu","family":"Saadat","sequence":"first","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF) University of Campania \u201cLuigi Vanvitelli\u201d  Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cecere","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF) University of Campania \u201cLuigi Vanvitelli\u201d  Caserta Italy"},{"name":"Institute of Genetics and Biophysics (IGB) \u201cAdriano Buzzati\u2010Traverso\u201d, Consiglio Nazionale delle Ricerche (CNR)  Naples Italy"},{"name":"UOS Laboratori di Ricerca e Biobanca, UOC Ricerca Clinica e Traslazionale, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Rossetti","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF) University of Campania \u201cLuigi Vanvitelli\u201d  Caserta 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\u201cLuigi Vanvitelli\u201d  Caserta Italy"},{"name":"Institute of Genetics and Biophysics (IGB) \u201cAdriano Buzzati\u2010Traverso\u201d, Consiglio Nazionale delle Ricerche (CNR)  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Verde","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF) University of Campania \u201cLuigi Vanvitelli\u201d  Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1940-7375","authenticated-orcid":false,"given":"Paola","family":"Quarello","sequence":"additional","affiliation":[{"name":"Pediatric Onco\u2010Haematology Division Regina Margherita Children's Hospital  Turin Italy"},{"name":"Department of Public Health and Pediatrics University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Fagioli","sequence":"additional","affiliation":[{"name":"Pediatric Onco\u2010Haematology Division Regina Margherita Children's Hospital  Turin Italy"},{"name":"Department of Public Health and Pediatrics University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Roma","sequence":"additional","affiliation":[{"name":"Childhood Cancer and Blood Disorders, Vall d'Hebron Research Institute (VHIR)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manel","family":"Esteller","sequence":"additional","affiliation":[{"name":"Cancer Epigenetics Group Josep Carreras Leukaemia Research Institute (IJC)  Badalona, Barcelona Catalonia Spain"},{"name":"Centro de Investigacion Biomedica en Red Cancer (CIBERONC)  Madrid Spain"},{"name":"Institucio Catalana de Recerca i Estudis Avan\u00e7ats (ICREA)  Barcelona Catalonia 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