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The genomic and transcriptional landscape of primary central nervous system lymphoma

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Item Type:Article
Title:The genomic and transcriptional landscape of primary central nervous system lymphoma
Creators Name:Radke, J. and Ishaque, N. and Koll, R. and Gu, Z. and Schumann, E. and Sieverling, L. and Uhrig, S. and Hübschmann, D. and Toprak, U.H. and López, C. and Hostench, X.P. and Borgoni, S. and Juraeva, D. and Pritsch, F. and Paramasivam, N. and Balasubramanian, G.P. and Schlesner, M. and Sahay, S. and Weniger, M. and Pehl, D. and Radbruch, H. and Osterloh, A. and Korfel, A. and Misch, M. and Onken, J. and Faust, K. and Vajkoczy, P. and Moskopp, D. and Wang, Y. and Jödicke, A. and Trümper, L. and Anagnostopoulos, I. and Lenze, D. and Küppers, R. and Hummel, M. and Schmitt, C.A. and Wiestler, O.D. and Wolf, S. and Unterberg, A. and Eils, R. and Herold-Mende, C. and Brors, B. and Siebert, R. and Wiemann, S. and Heppner, F.L.
Abstract: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.
Keywords:B-Cell Lymphoma, Cancer Genomics, CNS Cancer
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:2558
Date:10 May 2022
Official Publication:https://doi.org/10.1038/s41467-022-30050-y
PubMed:View item in PubMed

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