{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T19:34:19Z","timestamp":1776022459857,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"AIRC-Associazione Italiana Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 2020 ID 24405"],"award-info":[{"award-number":["IG 2020 ID 24405"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PON Ricerca e Innovazione 2014\u20132020 from Italian Ministry of University and Research","award":["IG 2020 ID 24405"],"award-info":[{"award-number":["IG 2020 ID 24405"]}]},{"name":"\u201cProgetti competitivi intraAteneo\u201d Programma V:ALERE","award":["IG 2020 ID 24405"],"award-info":[{"award-number":["IG 2020 ID 24405"]}]},{"name":"Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d","award":["IG 2020 ID 24405"],"award-info":[{"award-number":["IG 2020 ID 24405"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>CRC is an adult-onset carcinoma representing the third most common cancer and the second leading cause of cancer-related deaths in the world. EO-CRC (&lt;45 years of age) accounts for 5% of the CRC cases and is associated with cancer-predisposing genetic factors in half of them. Here, we describe the case of a woman affected by BWSp who developed EO-CRC at age 27. To look for a possible molecular link between BWSp and EO-CRC, we analysed her whole-genome genetic and epigenetic profiles in blood, and peri-neoplastic and neoplastic colon tissues. The results revealed a general instability of the tumor genome, including copy number and methylation changes affecting genes of the WNT signaling pathway, CRC biomarkers and imprinted loci. At the germline level, two missense mutations predicted to be likely pathogenic were found in compound heterozygosity affecting the Cystic Fibrosis (CF) gene CFTR that has been recently classified as a tumor suppressor gene, whose dysregulation represents a severe risk factor for developing CRC. We also detected constitutional loss of methylation of the KCNQ1OT1:TSS-DMR that leads to bi-allelic expression of the lncRNA KCNQ1OT1 and BWSp. Our results support the hypothesis that the inherited CFTR mutations, together with constitutional loss of methylation of the KCNQ1OT1:TSS-DMR, initiate the tumorigenesis process. Further somatic genetic and epigenetic changes enhancing the activation of the WNT\/beta-catenin pathway likely contributed to increase the growth advantage of cancer cells. Although this study does not provide any conclusive cause\u2013effect relationship between BWSp and CRC, it is tempting to speculate that the imprinting defect of BWSp might accelerate tumorigenesis in adult cancer in the presence of predisposing genetic variants.<\/jats:p>","DOI":"10.3390\/cancers15071944","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T02:34:54Z","timestamp":1679625294000},"page":"1944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Co-Occurrence of Beckwith\u2013Wiedemann Syndrome and Early-Onset Colorectal Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0329-0870","authenticated-orcid":false,"given":"Francesco","family":"Cecere","sequence":"first","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8835-5567","authenticated-orcid":false,"given":"Laura","family":"Pignata","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-183X","authenticated-orcid":false,"given":"Bruno","family":"Hay Mele","sequence":"additional","affiliation":[{"name":"Department of Biology, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80126 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abu","family":"Saadat","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-3482","authenticated-orcid":false,"given":"Orazio","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, 71013 San Giovanni Rotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9498-9902","authenticated-orcid":false,"given":"Pietro","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, 71013 San Giovanni Rotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-6829","authenticated-orcid":false,"given":"Massimo","family":"Carella","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, 71013 San Giovanni Rotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-0711","authenticated-orcid":false,"given":"Gioacchino","family":"Scarano","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Azienda Ospedaliera \u201cSan Pio\u201d P.\u201dGaetano Rummo\u201d, 82100 Benevento, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni Battista","family":"Rossi","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8350-8464","authenticated-orcid":false,"given":"Claudia","family":"Angelini","sequence":"additional","affiliation":[{"name":"Istituto per le Applicazioni del Calcolo (IAC) \u201cMauro Picone\u201d, Consiglio Nazionale delle Ricerche (CNR), 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4352-945X","authenticated-orcid":false,"given":"Angela","family":"Sparago","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3794-3021","authenticated-orcid":false,"given":"Flavia","family":"Cerrato","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7990-3576","authenticated-orcid":false,"given":"Andrea","family":"Riccio","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"},{"name":"Institute of Genetics and e Biophysics (IGB) \u201cAdriano Buzzati-Traverso\u201d, Consiglio Nazionale delle Ricerche (CNR), 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"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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