Epstein−Barr virus reactivation induces MYC-IGH spatial proximity and t(8;14) in B cells

Авторы: 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
Журнал: Journal of Medical Virology
Том: 95
Номер: 3
Год издания: 2023
Издательство: John Wiley & Sons Inc.
Местоположение издательства: United States
DOI: 10.1002/jmv.28633
Аннотация: 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.
Добавил в систему: Ломов Николай Андреевич

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