The genomic and transcriptional landscape of primary central nervous system lymphoma
2022 | journal article. A publication with affiliation to the University of Göttingen.
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The genomic and transcriptional landscape of primary central nervous system lymphoma
Radke, J.; Ishaque, N.; Koll, R.; Gu, Z.; Schumann, E.; Sieverling, L. & Uhrig, S. et al. (2022)
Nature Communications, 13(1) art. 2558. DOI: https://doi.org/10.1038/s41467-022-30050-y
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Details
- Authors Group
- ICGC MMML-Seq Consortium
The authors list is uncomplete: - Authors
- Radke, Josefine; Ishaque, Naveed; Koll, Randi; Gu, Zuguang; Schumann, Elisa; Sieverling, Lina; Uhrig, Sebastian; Hübschmann, Daniel; Toprak, Umut H.; López, Cristina; Heppner, Frank L.
- Abstract
- 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.
- Issue Date
- 2022
- Journal
- Nature Communications
- eISSN
- 2041-1723
- Language
- English