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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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
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spelling SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic featuresSureda-Gómez, MartaIaccarino, IngramBolòs, Anna deMeyer, MiekeBalsas, PatriciaRichter, JuliaRodríguez, Marta-LeonorLópez González, CristinaCarreras Caballé, MariaGlaser, SelinaNadeu Prat, FerranJares Gerboles, PedroClot Razquin, GuillemSiciliano, Maria ChiaraBellan, CristinaTornambè, SalvatoreBoccacci, RobertoLeoncini, LorenzoCampo Güerri, EliasSiebert, ReinerAmador Espinosa, VirginiaKlapper, WolframVirusDuplicació de l'ADNLimfomesFactors de transcripcióGenèticaVirusesDNA replicationLymphomasTranscription factorsGeneticsSRY-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.American Society of Hematology2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/221948Articles publicats en revistes (Fonaments Clínics)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1182/blood.2023023242Blood, 2024, vol. 144, num.2, p. 187-200https://doi.org/10.1182/blood.2023023242(c) American Society of Hematology, 2024info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2219482026-05-27T06:46:51Z
dc.title.none.fl_str_mv SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features
title SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features
spellingShingle SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features
Sureda-Gómez, Marta
Virus
Duplicació de l'ADN
Limfomes
Factors de transcripció
Genètica
Viruses
DNA replication
Lymphomas
Transcription factors
Genetics
title_short SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features
title_full SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features
title_fullStr SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features
title_full_unstemmed SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features
title_sort SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features
dc.creator.none.fl_str_mv 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
author Sureda-Gómez, Marta
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Virus
Duplicació de l'ADN
Limfomes
Factors de transcripció
Genètica
Viruses
DNA replication
Lymphomas
Transcription factors
Genetics
topic Virus
Duplicació de l'ADN
Limfomes
Factors de transcripció
Genètica
Viruses
DNA replication
Lymphomas
Transcription factors
Genetics
description 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.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/221948
url https://hdl.handle.net/2445/221948
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1182/blood.2023023242
Blood, 2024, vol. 144, num.2, p. 187-200
https://doi.org/10.1182/blood.2023023242
dc.rights.none.fl_str_mv (c) American Society of Hematology, 2024
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society of Hematology, 2024
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society of Hematology
publisher.none.fl_str_mv American Society of Hematology
dc.source.none.fl_str_mv Articles publicats en revistes (Fonaments Clínics)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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