{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:50:18Z","timestamp":1791561018662,"version":"4.3.4"},"reference-count":77,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"La Ligue Contre le Cancer","award":["GR-IARC-2014-04-07-03"],"award-info":[{"award-number":["GR-IARC-2014-04-07-03"]}]},{"name":"La Ligue Contre le Cancer","award":["OPE-2017-0009"],"award-info":[{"award-number":["OPE-2017-0009"]}]},{"name":"Oncostarter-(CLARA)","award":["GR-IARC-2014-05-15-02"],"award-info":[{"award-number":["GR-IARC-2014-05-15-02"]}]},{"name":"IARC Junior Award 2016","award":["AFEES-2016"],"award-info":[{"award-number":["AFEES-2016"]}]},{"name":"FWO Belgium","award":["G085921N"],"award-info":[{"award-number":["G085921N"]}]},{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","award":["ARCDOC42021020003117"],"award-info":[{"award-number":["ARCDOC42021020003117"]}],"id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Burkitt lymphoma (BL) is a malignant B cell neoplasm that accounts for almost half of pediatric cancers in sub-Saharan African countries. Although the BL endemic prevalence is attributable to the combination of Epstein\u2013Barr virus (EBV) infection with malaria and environmental carcinogens exposure, such as the food contaminant aflatoxin B1 (AFB1), the molecular determinants underlying the pathogenesis are not fully understood. Consistent with the role of epigenetic mechanisms at the interface between the genome and environment, AFB1 and EBV impact the methylome of respectively leukocytes and B cells specifically. Here, we conducted a thorough investigation of common epigenomic changes following EBV or AFB1 exposure in B cells. Genome-wide DNA methylation profiling identified an EBV\u2013AFB1 common signature within the TGFBI locus, which encodes for a putative tumor suppressor often altered in cancer. Subsequent mechanistic analyses confirmed a DNA-methylation-dependent transcriptional silencing of TGFBI involving the recruitment of DNMT1 methyltransferase that is associated with an activation of the NF-\u03baB pathway. Our results reveal a potential common mechanism of B cell transformation shared by the main risk factors of endemic BL (EBV and AFB1), suggesting a key determinant of disease that could allow the development of more efficient targeted therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cancers14051284","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T08:37:16Z","timestamp":1646210236000},"page":"1284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein\u2013Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development"],"prefix":"10.3390","volume":"14","author":[{"given":"Francesca","family":"Manara","sequence":"first","affiliation":[{"name":"International Agency for Research on Cancer, World Health Organization, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonin","family":"Jay","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, World Health Organization, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6180-4294","authenticated-orcid":false,"given":"Grace","family":"Odongo","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, World Health Organization, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5409-133X","authenticated-orcid":false,"given":"Fabrice","family":"Mure","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, RNA Expression in Viruses and Eukaryotes Group, Universite Claude Bernard Lyon I, INSERM U1111, CNRS UMR5308, ENS Lyon, 69007 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Maroui","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, RNA Expression in Viruses and Eukaryotes Group, Universite Claude Bernard Lyon I, INSERM U1111, CNRS UMR5308, ENS Lyon, 69007 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Diederichs","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, World Health Organization, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Sirand","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, World Health Organization, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrille","family":"Cuenin","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, World Health Organization, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Granai","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Section of Pathology, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Mundo","sequence":"additional","affiliation":[{"name":"Health Research Institute, University of Limerick, V94 T9PX Limerick, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-2103","authenticated-orcid":false,"given":"Hector","family":"Hernandez-Vargas","sequence":"additional","affiliation":[{"name":"Lyon Cancer Research Center (CRCL), INSERM U1052, Centre L\u00e9on B\u00e9rard, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Lazzi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Section of Pathology, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Khoueiry","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, World Health Organization, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4735-6894","authenticated-orcid":false,"given":"Henri","family":"Gruffat","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, RNA Expression in Viruses and Eukaryotes Group, Universite Claude Bernard Lyon I, INSERM U1111, CNRS UMR5308, ENS Lyon, 69007 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4109-3154","authenticated-orcid":false,"given":"Zdenko","family":"Herceg","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, World Health Organization, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosita","family":"Accardi","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, World Health Organization, 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1080\/07357900701805686","article-title":"The Role of Environmental Factors in the Etiology of Lymphoma","volume":"26","author":"Blinder","year":"2008","journal-title":"Cancer Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nri3814","article-title":"Germinal centres and B cell lymphomagenesis","volume":"15","author":"Basso","year":"2015","journal-title":"Nat. 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