Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development
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–Barr virus (EBV) infection with malaria and environmental carcinogens exposure, s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/5/1284 |
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| author | Francesca Manara Antonin Jay Grace Akinyi Odongo Fabrice Mure Mohamed Ali Maroui Audrey Diederichs Cecilia Sirand Cyrille Cuenin Massimo Granai Lucia Mundo Hector Hernandez-Vargas Stefano Lazzi Rita Khoueiry Henri Gruffat Zdenko Herceg Rosita Accardi |
| author_facet | Francesca Manara Antonin Jay Grace Akinyi Odongo Fabrice Mure Mohamed Ali Maroui Audrey Diederichs Cecilia Sirand Cyrille Cuenin Massimo Granai Lucia Mundo Hector Hernandez-Vargas Stefano Lazzi Rita Khoueiry Henri Gruffat Zdenko Herceg Rosita Accardi |
| author_sort | Francesca Manara |
| collection | DOAJ |
| description | 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–Barr 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–AFB1 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-κB 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. |
| first_indexed | 2024-03-09T20:44:36Z |
| format | Article |
| id | doaj.art-4c02977cad654ff2bd9c9b1078285aa0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:44:36Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4c02977cad654ff2bd9c9b1078285aa02023-11-23T22:48:41ZengMDPI AGCancers2072-66942022-03-01145128410.3390/cancers14051284Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma DevelopmentFrancesca Manara0Antonin Jay1Grace Akinyi Odongo2Fabrice Mure3Mohamed Ali Maroui4Audrey Diederichs5Cecilia Sirand6Cyrille Cuenin7Massimo Granai8Lucia Mundo9Hector Hernandez-Vargas10Stefano Lazzi11Rita Khoueiry12Henri Gruffat13Zdenko Herceg14Rosita Accardi15International Agency for Research on Cancer, World Health Organization, 69000 Lyon, FranceInternational Agency for Research on Cancer, World Health Organization, 69000 Lyon, FranceInternational Agency for Research on Cancer, World Health Organization, 69000 Lyon, FranceCIRI, 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, FranceCIRI, 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, FranceInternational Agency for Research on Cancer, World Health Organization, 69000 Lyon, FranceInternational Agency for Research on Cancer, World Health Organization, 69000 Lyon, FranceInternational Agency for Research on Cancer, World Health Organization, 69000 Lyon, FranceDepartment of Medical Biotechnology, Section of Pathology, University of Siena, 53100 Siena, ItalyHealth Research Institute, University of Limerick, V94 T9PX Limerick, IrelandLyon Cancer Research Center (CRCL), INSERM U1052, Centre Léon Bérard, 69000 Lyon, FranceDepartment of Medical Biotechnology, Section of Pathology, University of Siena, 53100 Siena, ItalyInternational Agency for Research on Cancer, World Health Organization, 69000 Lyon, FranceCIRI, 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, FranceInternational Agency for Research on Cancer, World Health Organization, 69000 Lyon, FranceInternational Agency for Research on Cancer, World Health Organization, 69000 Lyon, FranceBurkitt 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–Barr 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–AFB1 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-κB 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.https://www.mdpi.com/2072-6694/14/5/1284Burkitt lymphomaEBVAFB1DNA methylation |
| spellingShingle | Francesca Manara Antonin Jay Grace Akinyi Odongo Fabrice Mure Mohamed Ali Maroui Audrey Diederichs Cecilia Sirand Cyrille Cuenin Massimo Granai Lucia Mundo Hector Hernandez-Vargas Stefano Lazzi Rita Khoueiry Henri Gruffat Zdenko Herceg Rosita Accardi Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development Cancers Burkitt lymphoma EBV AFB1 DNA methylation |
| title | Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development |
| title_full | Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development |
| title_fullStr | Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development |
| title_full_unstemmed | Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development |
| title_short | Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development |
| title_sort | epigenetic alteration of the cancer related gene tgfbi in b cells infected with epstein barr virus and exposed to aflatoxin b1 potential role in burkitt lymphoma development |
| topic | Burkitt lymphoma EBV AFB1 DNA methylation |
| url | https://www.mdpi.com/2072-6694/14/5/1284 |
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