The genomic and transcriptional landscape of primary central nervous system lymphoma
Creators: name: Radke, Josefine
name: Ishaque, Naveed
name: Koll, Randi
name: Gu, Zuguang
name: Schumann, Elisa
name: Sieverling, Lina
name: Uhrig, Sebastian
name: Hübschmann, Daniel
name: Toprak, Umut H.
name: López, Cristina
name: Hostench, Xavier Pastor
name: Borgoni, Simone
name: Juraeva, Dilafruz
name: Pritsch, Fabienne
name: Paramasivam, Nagarajan
name: Balasubramanian, Gnana Prakash
name: Schlesner, Matthias
name: Sahay, Shashwat
name: Weniger, Marc
name: Pehl, Debora
name: Radbruch, Helena
name: Osterloh, Anja
name: Korfel, Agnieszka
name: Misch, Martin
name: Onken, Julia
name: Faust, Katharina
name: Vajkoczy, Peter
name: Moskopp, Dag
name: Wang, Yawen
name: Jödicke, Andreas
name: Trümper, Lorenz
name: Anagnostopoulos, Ioannis
name: Lenze, Dido
name: Küppers, Ralf
name: Hummel, Michael
name: Schmitt, Clemens A.
name: Wiestler, Otmar D.
name: Wolf, Stephan
name: Unterberg, Andreas
name: Eils, Roland
name: Herold-Mende, Christel
name: Brors, Benedikt
name: Siebert, Reiner
name: Wagner, Susanne
name: Haake, Andrea
name: Richter, Julia
name: Richter, Gesine
name: Eils, Roland
name: Lawerenz, Chris
name: Eils, Jürgen
name: Kerssemakers, Jules
name: Jaeger-Schmidt, Christina
name: Scholz, Ingrid
name: Bergmann, Anke K.
name: Borst, Christoph
name: Braulke, Friederike
name: Burkhardt, Birgit
name: Claviez, Alexander
name: Dreyling, Martin
name: Eberth, Sonja
name: Einsele, Hermann
name: Frickhofen, Norbert
name: Haas, Siegfried
name: Hansmann, Martin-Leo
name: Karsch, Dennis
name: Klepl, Nicole
name: Kneba, Michael
name: Lisfeld, Jasmin
name: Mantovani-Löffler, Luisa
name: Rohde, Marius
name: Ott, German
name: Stadler, Christina
name: Staib, Peter
name: Stilgenbauer, Stephan
name: Zenz, Thorsten
name: Hansmann, Martin-Leo
name: Kube, Dieter
name: Haas, Siegfried
name: Klapper, Wolfram
name: Kostezka, Ulrike
name: Möller, Peter
name: Rosenwald, Andreas
name: Ott, German
name: Szczepanowski, Monika
name: Ammerpohl, Ole
name: Aukema, Sietse M.
name: Binder, Vera
name: Borkhardt, Arndt
name: Haake, Andrea
name: Hoell, Jessica I.
name: Leich, Ellen
name: Lichter, Peter
name: López, Cristina
name: Nagel, Inga
name: Pischimariov, Jordan
name: Radlwimmer, Bernhard
name: Richter, Julia
name: Rosenstiel, Philip
name: Rosenwald, Andreas
name: Schilhabel, Markus
name: Schreiber, Stefan
name: Vater, Inga
name: Wagener, Rabea
name: Siebert, Reiner
name: Bernhart, Stephan H.
name: Binder, Hans
name: Doose, Gero
name: Eils, Roland
name: Hoffmann, Steve
name: Hopp, Lydia
name: Kleinheinz, Kortine
name: Kretzmer, Helene
name: Kreuz, Markus
name: Korbel, Jan
name: Langenberger, David
name: Loeffler, Markus
name: Rosolowski, Maciej
name: Stadler, Peter F.
name: Sungalee, Stephanie
name: Siebert, Reiner
name: Wiemann, Stefan
name: Heppner, Frank L.
name: ICGC MMML-Seq Consortium
name: Coordination (C1)
name: Data Center (C2)
name: Clinical Centers (WP1)
name: Normal Cells (WPN)
name: Pathology And Analyte Preparation (WP2-3)
name: Sequencing And Genomics (WP4-7)
name: Bioinformatics (WP8-9)
Publisher: name: Charité - Universitätsmedizin Berlin
Year: 2022
Subjects: subject: central nervous system
subject: primary lymphomas
subject: Lymphoma, Large B-Cell
subject: 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit

description: 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.