Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements

Diffuse large B-cell lymphoma (DLBCL) with aberrant co-expression of CD10+BCL6+MUM1+ (DLBCL-AE), classified as germinal center B cell (GCB)-type by the Hans algorithm (HA), were genetically characterized. To capture the complexity of these DLBCL-AE, we used an integrated approach including gene expr...

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Autores: Frauenfeld, Leonie, Castrejón de Anta, Natalia, Ramis Zaldívar, Joan Enric, Streich, Sebastian, Salmerón Villalobos, Julia, Otto, Franziska, Mayer, Annika Katharina, Steinhilber, Julia, Pinyol, Magda, Mankel, Barbara, Ramsower, Colleen, Bonzheim, Irina, Fend, Falko, Rimsza, Lisa, Salaverria Lete, Itziar, Campo Güerri, Elias, Balague, Olga, Quintanilla Martinez, Leticia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/199465
Acceso en línea:https://hdl.handle.net/2445/199465
Access Level:acceso abierto
Palabra clave:Limfomes
Genètica mèdica
Lymphomas
Medical genetics
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spelling Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangementsFrauenfeld, LeonieCastrejón de Anta, NataliaRamis Zaldívar, Joan EnricStreich, SebastianSalmerón Villalobos, JuliaOtto, FranziskaMayer, Annika KatharinaSteinhilber, JuliaPinyol, MagdaMankel, BarbaraRamsower, ColleenBonzheim, IrinaFend, FalkoRimsza, LisaSalaverria Lete, ItziarCampo Güerri, EliasBalague, OlgaQuintanilla Martinez, LeticiaLimfomesGenètica mèdicaLymphomasMedical geneticsDiffuse large B-cell lymphoma (DLBCL) with aberrant co-expression of CD10+BCL6+MUM1+ (DLBCL-AE), classified as germinal center B cell (GCB)-type by the Hans algorithm (HA), were genetically characterized. To capture the complexity of these DLBCL-AE, we used an integrated approach including gene expression profiling (GEP), fluorescence in-situ hybridization (FISH), targeted gene sequencing, and copy number (CN) arrays. According to GEP, 32/54 (59%) cases were classified as GCB-DLBCL, 16/54 (30%) as activated B-cell (ABC)-DLBCL and 6/54 (11%) as unclassifiable. The discrepancy between HA and GEP was 41%. Three genetic subgroups were identified. Group 1 included 13/50 (26%) cases without translocations and mainly showing and ABC/MCD molecular profile. Group 2 comprised 11/50 (22%) cases with IRF4 alterations (DLBCL-IRF4), frequent mutations in IRF4 (82%) and NF-?B pathway genes (MYD88, CARD11, and CD79B), and losses of 17p13.2. Five cases each were classified as GCB- or ABC-type. Group 3 included 26/50 (52%) cases with one or several translocations in BCL2/BCL6/MYC/IGH and GCB/EZB molecular profile predominated. Two cases in this latter group showed complex BCL2/BCL6/IRF4 translocations. DLBCL-IRF4 in adults showed a similar CN profile and share recurrent CARD11 and CD79B mutations when compared to LBCL-IRF4 in pediatric population. However, adult cases showed higher genetic complexity, higher mutational load with frequent MYD88 and KMT2D mutations, and more often ABC-GEP. IRF4 mutations were identified only in IRF4-rearranged cases indicating its potential utility in the diagnostic setting. In conclusion, DLBCL-AE are genetically heterogeneous and enriched in cases with IRF4 alterations. DLBCL-IRF4 in adults has many similarities to the pediatric counterpart.Copyright © 2021 American Society of Hematology.American Society of Hematology2023202320212023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/199465Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1182/bloodadvances.2021006034Blood Advances, 2022, vol. 6, num. 7, p. 2361-2372https://doi.org/10.1182/bloodadvances.2021006034cc by-nc-nd (c) Frauenfeld, Leonie et al, 2022http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1994652026-05-29T05:05:01Z
dc.title.none.fl_str_mv Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements
title Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements
spellingShingle Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements
Frauenfeld, Leonie
Limfomes
Genètica mèdica
Lymphomas
Medical genetics
title_short Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements
title_full Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements
title_fullStr Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements
title_full_unstemmed Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements
title_sort Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements
dc.creator.none.fl_str_mv Frauenfeld, Leonie
Castrejón de Anta, Natalia
Ramis Zaldívar, Joan Enric
Streich, Sebastian
Salmerón Villalobos, Julia
Otto, Franziska
Mayer, Annika Katharina
Steinhilber, Julia
Pinyol, Magda
Mankel, Barbara
Ramsower, Colleen
Bonzheim, Irina
Fend, Falko
Rimsza, Lisa
Salaverria Lete, Itziar
Campo Güerri, Elias
Balague, Olga
Quintanilla Martinez, Leticia
author Frauenfeld, Leonie
author_facet Frauenfeld, Leonie
Castrejón de Anta, Natalia
Ramis Zaldívar, Joan Enric
Streich, Sebastian
Salmerón Villalobos, Julia
Otto, Franziska
Mayer, Annika Katharina
Steinhilber, Julia
Pinyol, Magda
Mankel, Barbara
Ramsower, Colleen
Bonzheim, Irina
Fend, Falko
Rimsza, Lisa
Salaverria Lete, Itziar
Campo Güerri, Elias
Balague, Olga
Quintanilla Martinez, Leticia
author_role author
author2 Castrejón de Anta, Natalia
Ramis Zaldívar, Joan Enric
Streich, Sebastian
Salmerón Villalobos, Julia
Otto, Franziska
Mayer, Annika Katharina
Steinhilber, Julia
Pinyol, Magda
Mankel, Barbara
Ramsower, Colleen
Bonzheim, Irina
Fend, Falko
Rimsza, Lisa
Salaverria Lete, Itziar
Campo Güerri, Elias
Balague, Olga
Quintanilla Martinez, Leticia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Limfomes
Genètica mèdica
Lymphomas
Medical genetics
topic Limfomes
Genètica mèdica
Lymphomas
Medical genetics
description Diffuse large B-cell lymphoma (DLBCL) with aberrant co-expression of CD10+BCL6+MUM1+ (DLBCL-AE), classified as germinal center B cell (GCB)-type by the Hans algorithm (HA), were genetically characterized. To capture the complexity of these DLBCL-AE, we used an integrated approach including gene expression profiling (GEP), fluorescence in-situ hybridization (FISH), targeted gene sequencing, and copy number (CN) arrays. According to GEP, 32/54 (59%) cases were classified as GCB-DLBCL, 16/54 (30%) as activated B-cell (ABC)-DLBCL and 6/54 (11%) as unclassifiable. The discrepancy between HA and GEP was 41%. Three genetic subgroups were identified. Group 1 included 13/50 (26%) cases without translocations and mainly showing and ABC/MCD molecular profile. Group 2 comprised 11/50 (22%) cases with IRF4 alterations (DLBCL-IRF4), frequent mutations in IRF4 (82%) and NF-?B pathway genes (MYD88, CARD11, and CD79B), and losses of 17p13.2. Five cases each were classified as GCB- or ABC-type. Group 3 included 26/50 (52%) cases with one or several translocations in BCL2/BCL6/MYC/IGH and GCB/EZB molecular profile predominated. Two cases in this latter group showed complex BCL2/BCL6/IRF4 translocations. DLBCL-IRF4 in adults showed a similar CN profile and share recurrent CARD11 and CD79B mutations when compared to LBCL-IRF4 in pediatric population. However, adult cases showed higher genetic complexity, higher mutational load with frequent MYD88 and KMT2D mutations, and more often ABC-GEP. IRF4 mutations were identified only in IRF4-rearranged cases indicating its potential utility in the diagnostic setting. In conclusion, DLBCL-AE are genetically heterogeneous and enriched in cases with IRF4 alterations. DLBCL-IRF4 in adults has many similarities to the pediatric counterpart.Copyright © 2021 American Society of Hematology.
publishDate 2021
dc.date.none.fl_str_mv 2021
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/199465
url https://hdl.handle.net/2445/199465
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1182/bloodadvances.2021006034
Blood Advances, 2022, vol. 6, num. 7, p. 2361-2372
https://doi.org/10.1182/bloodadvances.2021006034
dc.rights.none.fl_str_mv cc by-nc-nd (c) Frauenfeld, Leonie et al, 2022
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Frauenfeld, Leonie et al, 2022
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
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 (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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