Epstein−Barr virus reactivation induces MYC‐IGH spatial proximity and t(8;14) in B cells
In: ISSN: 0146-6615, 2023
Online
academicJournal
Zugriff:
Burkitt lymphoma (BL) is a B cell malignancy associated with the Epstein−Barr virus (EBV). Most BL cases are characterized by a t(8;14) chromosomal translocation involving the MYC oncogene and the immunoglobulin heavy chain gene ( IGH ). The role of EBV in promoting this translocation remains largely unknown. Here we provide the experimental evidence that EBV reactivation from latency leads to an increase in the proximity between the MYC and IGH loci, otherwise located far away in the nuclear space both in B‐lymphoblastoid cell lines and in patients' B‐cells. Specific DNA damage within the MYC locus, followed by the MRE11‐dependent DNA repair plays a role in this process. Using a CRISPR/Cas9‐based B cell model to induce specific DNA double strand breaks in MYC and IGH loci, we have shown that the MYC‐IGH proximity induced by EBV reactivation leads to an increased t(8;14) translocation frequency.
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Epstein−Barr virus reactivation induces MYC‐IGH spatial proximity and t(8;14) in B cells
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| Autor/in / Beteiligte Person: | Sall, Fatimata Bintou ; Shmakova, Anna ; Karpukhina, Anna ; Tsfasman, Tatyana ; Lomov, Nikolai ; Canoy, Reynand Jay ; Boutboul, David ; Oksenhendler, Eric ; Toure, Awa Oumar ; Lipinski, Marc ; Wiels, Joëlle ; Germini, Diego ; Vassetzky, Yegor ; Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques (METSY) ; Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) ; Université Cheikh Anta Diop de Dakar Sénégal (UCAD) ; Koltzov Institute of Developmental Biology ; the Russian Academy of Sciences Moscow, Russia (RAS) ; Hopital Saint-Louis AP-HP (AP-HP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) ; Immunologie clinique CHU St-Louis ; Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) ; Université Paris Cité (UPCité) ; Institut Gustave Roussy (IGR) |
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| Zeitschrift: | ISSN: 0146-6615, 2023 |
| Veröffentlichung: | HAL CCSD ; Wiley-Blackwell, 2023 |
| Medientyp: | academicJournal |
| DOI: | 10.1002/jmv.28633 |
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