Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma
B-cell lymphoma; Cancer genetics
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Departament de Salut de la Generalitat de Catalunya (DS) |
| Repositorio: | Scientia. Dipòsit d'Informació Digital del Departament de Salut |
| OAI Identifier: | oai:scientiasalut.gencat.cat:11351/7391 |
| Acceso en línea: | https://hdl.handle.net/11351/7391 |
| Access Level: | acceso abierto |
| Palabra clave: | Cèl·lules B - Tumors - Tractament Seqüència de nucleòtids Sistema limfàtic - Càncer - Mortalitat DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse::Plasmablastic Lymphoma Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::Whole Genome Sequencing::Whole Exome Sequencing ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso::linfoma plasmablástico Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN::secuenciación del genoma completo::secuenciación del exoma completo |
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Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphomaStaiger, Annette M.Zapukhlyak, MyroslavXu, WendanBonzheim, IrinaBorgmann, VanessaCastellví Vives, JosepAbrisqueta Costa, PabloFrontzek, FabianCèl·lules B - Tumors - TractamentSeqüència de nucleòtidsSistema limfàtic - Càncer - MortalitatDISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse::Plasmablastic LymphomaOther subheadings::Other subheadings::/therapyANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::Whole Genome Sequencing::Whole Exome SequencingENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso::linfoma plasmablásticoOtros calificadores::Otros calificadores::/terapiaTÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN::secuenciación del genoma completo::secuenciación del exoma completoB-cell lymphoma; Cancer geneticsLinfoma de células B; Genética del cáncerLimfoma de cèl·lules B; Genètica del càncerPlasmablastic lymphoma (PBL) represents a rare and aggressive lymphoma subtype frequently associated with immunosuppression. Clinically, patients with PBL are characterized by poor outcome. The current understanding of the molecular pathogenesis is limited. A hallmark of PBL represents its plasmacytic differentiation with loss of B-cell markers and, in 60% of cases, its association with Epstein-Barr virus (EBV). Roughly 50% of PBLs harbor a MYC translocation. Here, we provide a comprehensive integrated genomic analysis using whole exome sequencing (WES) and genome-wide copy number determination in a large cohort of 96 primary PBL samples. We identify alterations activating the RAS-RAF, JAK-STAT, and NOTCH pathways as well as frequent high-level amplifications in MCL1 and IRF4. The functional impact of these alterations is assessed using an unbiased shRNA screen in a PBL model. These analyses identify the IRF4 and JAK-STAT pathways as promising molecular targets to improve outcome of PBL patients.Open Access funding enabled and organized by Projekt DEAL.Nature ResearchInstitut Català de la Salut[Frontzek F, Zapukhlyak M, Xu W] Department of Medicine A, Department of Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany. [Staiger AM] Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tuebingen, Tübingen, Germany. Department of Clinical Pathology, Robert Bosch Hospital, Stuttgart, Germany. [Bonzheim I, Borgmann V] Institute of Pathology and Neuropathology, Eberhard Karls University of TübingenComprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany. [Castellvi J] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Abrisqueta P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202220222021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/7391Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésNature Communications;12https://doi.org/10.1038/s41467-021-25405-wAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/73912026-06-12T09:38:37Z |
| dc.title.none.fl_str_mv |
Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma |
| title |
Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma |
| spellingShingle |
Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma Staiger, Annette M. Cèl·lules B - Tumors - Tractament Seqüència de nucleòtids Sistema limfàtic - Càncer - Mortalitat DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse::Plasmablastic Lymphoma Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::Whole Genome Sequencing::Whole Exome Sequencing ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso::linfoma plasmablástico Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN::secuenciación del genoma completo::secuenciación del exoma completo |
| title_short |
Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma |
| title_full |
Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma |
| title_fullStr |
Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma |
| title_full_unstemmed |
Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma |
| title_sort |
Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma |
| dc.creator.none.fl_str_mv |
Staiger, Annette M. Zapukhlyak, Myroslav Xu, Wendan Bonzheim, Irina Borgmann, Vanessa Castellví Vives, Josep Abrisqueta Costa, Pablo Frontzek, Fabian |
| author |
Staiger, Annette M. |
| author_facet |
Staiger, Annette M. Zapukhlyak, Myroslav Xu, Wendan Bonzheim, Irina Borgmann, Vanessa Castellví Vives, Josep Abrisqueta Costa, Pablo Frontzek, Fabian |
| author_role |
author |
| author2 |
Zapukhlyak, Myroslav Xu, Wendan Bonzheim, Irina Borgmann, Vanessa Castellví Vives, Josep Abrisqueta Costa, Pablo Frontzek, Fabian |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
Institut Català de la Salut [Frontzek F, Zapukhlyak M, Xu W] Department of Medicine A, Department of Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany. [Staiger AM] Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tuebingen, Tübingen, Germany. Department of Clinical Pathology, Robert Bosch Hospital, Stuttgart, Germany. [Bonzheim I, Borgmann V] Institute of Pathology and Neuropathology, Eberhard Karls University of TübingenComprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany. [Castellvi J] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Abrisqueta P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus |
| dc.subject.none.fl_str_mv |
Cèl·lules B - Tumors - Tractament Seqüència de nucleòtids Sistema limfàtic - Càncer - Mortalitat DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse::Plasmablastic Lymphoma Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::Whole Genome Sequencing::Whole Exome Sequencing ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso::linfoma plasmablástico Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN::secuenciación del genoma completo::secuenciación del exoma completo |
| topic |
Cèl·lules B - Tumors - Tractament Seqüència de nucleòtids Sistema limfàtic - Càncer - Mortalitat DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse::Plasmablastic Lymphoma Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::Whole Genome Sequencing::Whole Exome Sequencing ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso::linfoma plasmablástico Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN::secuenciación del genoma completo::secuenciación del exoma completo |
| description |
B-cell lymphoma; Cancer genetics |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2022 2022 |
| 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/11351/7391 |
| url |
https://hdl.handle.net/11351/7391 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Nature Communications;12 https://doi.org/10.1038/s41467-021-25405-w |
| dc.rights.none.fl_str_mv |
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf application/pdf application/pdf application/pdf |
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Nature Research |
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Nature Research |
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Scientia reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut instname:Departament de Salut de la Generalitat de Catalunya (DS) |
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Departament de Salut de la Generalitat de Catalunya (DS) |
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Scientia. Dipòsit d'Informació Digital del Departament de Salut |
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Scientia. Dipòsit d'Informació Digital del Departament de Salut |
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1869403426448736256 |
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15.812455 |