The genomic and transcriptional landscape of primary central nervous system lymphoma
© 2022. The Author(s)..
Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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Enthalten in: |
Nature communications - 13(2022), 1 vom: 10. Mai, Seite 2558 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Radke, Josefine [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 12.05.2022 Date Revised 16.07.2022 published: Electronic Citation Status MEDLINE |
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doi: |
10.1038/s41467-022-30050-y |
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funding: |
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PPN (Katalog-ID): |
NLM340662689 |
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100 | 1 | |a Radke, Josefine |e verfasserin |4 aut | |
245 | 1 | 4 | |a The genomic and transcriptional landscape of primary central nervous system lymphoma |
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520 | |a Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
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700 | 1 | |a Hostench, Xavier Pastor |e verfasserin |4 aut | |
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700 | 1 | |a Juraeva, Dilafruz |e verfasserin |4 aut | |
700 | 1 | |a Pritsch, Fabienne |e verfasserin |4 aut | |
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700 | 1 | |a Jaeger-Schmidt, Christina |e investigator |4 oth | |
700 | 1 | |a Scholz, Ingrid |e investigator |4 oth | |
700 | 1 | |a Bergmann, Anke K |e investigator |4 oth | |
700 | 1 | |a Borst, Christoph |e investigator |4 oth | |
700 | 1 | |a Braulke, Friederike |e investigator |4 oth | |
700 | 1 | |a Burkhardt, Birgit |e investigator |4 oth | |
700 | 1 | |a Claviez, Alexander |e investigator |4 oth | |
700 | 1 | |a Dreyling, Martin |e investigator |4 oth | |
700 | 1 | |a Eberth, Sonja |e investigator |4 oth | |
700 | 1 | |a Einsele, Hermann |e investigator |4 oth | |
700 | 1 | |a Frickhofen, Norbert |e investigator |4 oth | |
700 | 1 | |a Haas, Siegfried |e investigator |4 oth | |
700 | 1 | |a Hansmann, Martin-Leo |e investigator |4 oth | |
700 | 1 | |a Karsch, Dennis |e investigator |4 oth | |
700 | 1 | |a Klepl, Nicole |e investigator |4 oth | |
700 | 1 | |a Kneba, Michael |e investigator |4 oth | |
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700 | 1 | |a Rohde, Marius |e investigator |4 oth | |
700 | 1 | |a Ott, German |e investigator |4 oth | |
700 | 1 | |a Stadler, Christina |e investigator |4 oth | |
700 | 1 | |a Staib, Peter |e investigator |4 oth | |
700 | 1 | |a Stilgenbauer, Stephan |e investigator |4 oth | |
700 | 1 | |a Zenz, Thorsten |e investigator |4 oth | |
700 | 1 | |a Hansmann, Martin-Leo |e investigator |4 oth | |
700 | 1 | |a Kube, Dieter |e investigator |4 oth | |
700 | 1 | |a Haas, Siegfried |e investigator |4 oth | |
700 | 1 | |a Klapper, Wolfram |e investigator |4 oth | |
700 | 1 | |a Kostezka, Ulrike |e investigator |4 oth | |
700 | 1 | |a Möller, Peter |e investigator |4 oth | |
700 | 1 | |a Rosenwald, Andreas |e investigator |4 oth | |
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700 | 1 | |a Aukema, Sietse M |e investigator |4 oth | |
700 | 1 | |a Binder, Vera |e investigator |4 oth | |
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700 | 1 | |a Pischimariov, Jordan |e investigator |4 oth | |
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700 | 1 | |a Rosenstiel, Philip |e investigator |4 oth | |
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700 | 1 | |a Bernhart, Stephan H |e investigator |4 oth | |
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700 | 1 | |a Doose, Gero |e investigator |4 oth | |
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700 | 1 | |a Hoffmann, Steve |e investigator |4 oth | |
700 | 1 | |a Hopp, Lydia |e investigator |4 oth | |
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700 | 1 | |a Sungalee, Stephanie |e investigator |4 oth | |
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