SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features

SRY-related HMG-box gene 11 (SOX11) is a transcription factor overexpressed in mantle cell lymphoma (MCL), a subset of Burkitt lymphomas (BL) and precursor lymphoid cell neoplasms but is absent in normal B cells and other B-cell lymphomas. SOX11 has an oncogenic role in MCL but its contribution to B...

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Detalles Bibliográficos
Autores: Sureda-Gómez, Marta, Iaccarino, Ingram, Bolòs, Anna de, Meyer, Mieke, Balsas, Patricia, Richter, Julia, Rodríguez, Marta-Leonor, López González, Cristina, Carreras Caballé, Maria, Glaser, Selina, Nadeu Prat, Ferran, Jares Gerboles, Pedro, Clot Razquin, Guillem, Siciliano, Maria Chiara, Bellan, Cristina, Tornambè, Salvatore, Boccacci, Roberto, Leoncini, Lorenzo, Campo Güerri, Elias, Siebert, Reiner, Amador Espinosa, Virginia, Klapper, Wolfram
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/221948
Acceso en línea:https://hdl.handle.net/2445/221948
Access Level:acceso abierto
Palabra clave:Virus
Duplicació de l'ADN
Limfomes
Factors de transcripció
Genètica
Viruses
DNA replication
Lymphomas
Transcription factors
Genetics
Descripción
Sumario:SRY-related HMG-box gene 11 (SOX11) is a transcription factor overexpressed in mantle cell lymphoma (MCL), a subset of Burkitt lymphomas (BL) and precursor lymphoid cell neoplasms but is absent in normal B cells and other B-cell lymphomas. SOX11 has an oncogenic role in MCL but its contribution to BL pathogenesis remains uncertain. Here, we observed that the presence of Epstein-Barr virus (EBV) and SOX11 expression were mutually exclusive in BL. SOX11 expression in EBV-negative (EVB-) BL was associated with an IG∷MYC translocation generated by aberrant class switch recombination, whereas in EBV-negative (EBV-)/SOX11-negative (SOX11-) tumors the IG∷MYC translocation was mediated by mistaken somatic hypermutations. Interestingly, EBV- SOX11-expressing BL showed higher frequency of SMARCA4 and ID3 mutations than EBV-/SOX11- cases. By RNA sequencing, we identified a SOX11-associated gene expression profile, with functional annotations showing partial overlap with the SOX11 transcriptional program of MCL. Contrary to MCL, no differences on cell migration or B-cell receptor signaling were found between SOX11- and SOX11-positive (SOX11+) BL cells. However, SOX11+ BL showed higher adhesion to vascular cell adhesion molecule 1 (VCAM-1) than SOX11- BL cell lines. Here, we demonstrate that EBV- BL comprises 2 subsets of cases based on SOX11 expression. The mutual exclusion of SOX11 and EBV, and the association of SOX11 with a specific genetic landscape suggest a role of SOX11 in the early pathogenesis of BL.

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