The genomic and transcriptional landscape of primary central nervous system lymphoma.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 05 2022
10 05 2022
Historique:
received:
19
08
2021
accepted:
12
04
2022
entrez:
10
5
2022
pubmed:
11
5
2022
medline:
14
5
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35538064
doi: 10.1038/s41467-022-30050-y
pii: 10.1038/s41467-022-30050-y
pmc: PMC9091224
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2558Investigateurs
Reiner Siebert
(R)
Susanne Wagner
(S)
Andrea Haake
(A)
Julia Richter
(J)
Gesine Richter
(G)
Roland Eils
(R)
Chris Lawerenz
(C)
Jürgen Eils
(J)
Jules Kerssemakers
(J)
Christina Jaeger-Schmidt
(C)
Ingrid Scholz
(I)
Anke K Bergmann
(AK)
Christoph Borst
(C)
Friederike Braulke
(F)
Birgit Burkhardt
(B)
Alexander Claviez
(A)
Martin Dreyling
(M)
Sonja Eberth
(S)
Hermann Einsele
(H)
Norbert Frickhofen
(N)
Siegfried Haas
(S)
Martin-Leo Hansmann
(ML)
Dennis Karsch
(D)
Nicole Klepl
(N)
Michael Kneba
(M)
Jasmin Lisfeld
(J)
Luisa Mantovani-Löffler
(L)
Marius Rohde
(M)
German Ott
(G)
Christina Stadler
(C)
Peter Staib
(P)
Stephan Stilgenbauer
(S)
Thorsten Zenz
(T)
Martin-Leo Hansmann
(ML)
Dieter Kube
(D)
Siegfried Haas
(S)
Wolfram Klapper
(W)
Ulrike Kostezka
(U)
Peter Möller
(P)
Andreas Rosenwald
(A)
German Ott
(G)
Monika Szczepanowski
(M)
Ole Ammerpohl
(O)
Sietse M Aukema
(SM)
Vera Binder
(V)
Arndt Borkhardt
(A)
Andrea Haake
(A)
Jessica I Hoell
(JI)
Ellen Leich
(E)
Peter Lichter
(P)
Cristina López
(C)
Inga Nagel
(I)
Jordan Pischimariov
(J)
Bernhard Radlwimmer
(B)
Julia Richter
(J)
Philip Rosenstiel
(P)
Andreas Rosenwald
(A)
Markus Schilhabel
(M)
Stefan Schreiber
(S)
Inga Vater
(I)
Rabea Wagener
(R)
Reiner Siebert
(R)
Stephan H Bernhart
(SH)
Hans Binder
(H)
Gero Doose
(G)
Roland Eils
(R)
Steve Hoffmann
(S)
Lydia Hopp
(L)
Kortine Kleinheinz
(K)
Helene Kretzmer
(H)
Markus Kreuz
(M)
Jan Korbel
(J)
David Langenberger
(D)
Markus Loeffler
(M)
Maciej Rosolowski
(M)
Peter F Stadler
(PF)
Stephanie Sungalee
(S)
Informations de copyright
© 2022. The Author(s).
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