Genomic insights into the pathogenesis of Epstein–Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing

  1. Gebauer, Niklas ORCID logo
  2. Künstner, Axel ORCID logo
  3. Ketzer, Julius
  4. WITTE, HANNO ORCID logo
  5. Rausch, Tobias ORCID logo
  6. Benes, Vladimir ORCID logo
  7. Zimmermann, Jürgen
  8. Gebauer, Judith
  9. Merz, Hartmut
  10. Bernard, Veronica
  11. Harder, Lana
  12. Ratjen, Katharina
  13. Gesk, Stefan
  14. Peter, Wolfgang
  15. Busch, Yannik
  16. Trojok, Peter
  17. von Bubnoff, Nikolas von Bubnoff ORCID logo
  18. Biersack, Harald
  19. Busch, Hauke
  20. Feller, Alfred C.

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1000 Titel
  • Genomic insights into the pathogenesis of Epstein–Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing
1000 Autor/in
  1. Gebauer, Niklas |
  2. Künstner, Axel |
  3. Ketzer, Julius |
  4. WITTE, HANNO |
  5. Rausch, Tobias |
  6. Benes, Vladimir |
  7. Zimmermann, Jürgen |
  8. Gebauer, Judith |
  9. Merz, Hartmut |
  10. Bernard, Veronica |
  11. Harder, Lana |
  12. Ratjen, Katharina |
  13. Gesk, Stefan |
  14. Peter, Wolfgang |
  15. Busch, Yannik |
  16. Trojok, Peter |
  17. von Bubnoff, Nikolas von Bubnoff |
  18. Biersack, Harald |
  19. Busch, Hauke |
  20. Feller, Alfred C. |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-05-26
1000 Erschienen in
1000 Quellenangabe
  • 11(5):102
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41408-021-00493-5 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155002/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Epstein-Barr virus (EBV)-associated diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) constitute a distinct clinicopathological entity in the current World Health Organization (WHO) classification. However, its genomic features remain sparsely characterized. Here, we combine whole-genome sequencing (WGS), targeted amplicon sequencing (tNGS), and fluorescence in situ hybridization (FISH) from 47 EBV + DLBCL (NOS) cases to delineate the genomic landscape of this rare disease. Integrated WGS and tNGS analysis clearly distinguished this tumor type from EBV-negative DLBCL due to frequent mutations in ARID1A (45%), KMT2A/KMT2D (32/30%), ANKRD11 (32%), or NOTCH2 (32%). WGS uncovered structural aberrations including 6q deletions (5/8 patients), which were subsequently validated by FISH (14/32 cases). Expanding on previous reports, we identified recurrent alterations in CCR6 (15%), DAPK1 (15%), TNFRSF21 (13%), CCR7 (11%), and YY1 (6%). Lastly, functional annotation of the mutational landscape by sequential gene set enrichment and network propagation predicted an effect on the nuclear factor κB (NFκB) pathway (CSNK2A2, CARD10), IL6/JAK/STAT (SOCS1/3, STAT3), and WNT signaling (FRAT1, SFRP5) alongside aberrations in immunological processes, such as interferon response. This first comprehensive description of EBV + DLBCL (NOS) tumors substantiates the evidence of its pathobiological independence and helps stratify the molecular taxonomy of aggressive lymphomas in the effort for future therapeutic strategies.
1000 Sacherschließung
lokal Chromosome Aberrations [MeSH]
lokal Female [MeSH]
lokal Mutation [MeSH]
lokal Aged, 80 and over [MeSH]
lokal Epstein-Barr Virus Infections/complications [MeSH]
lokal Lymphoma, Large B-Cell, Diffuse/genetics [MeSH]
lokal Whole Genome Sequencing [MeSH]
lokal Aged [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Lymphoma, Large B-Cell, Diffuse/virology [MeSH]
lokal Middle Aged [MeSH]
lokal Herpesvirus 4, Human/isolation
lokal Article
lokal Cytogenetics
lokal Male [MeSH]
lokal Gene Regulatory Networks [MeSH]
lokal Young Adult [MeSH]
lokal Cancer genomics
lokal In Situ Hybridization, Fluorescence [MeSH]
lokal High-Throughput Nucleotide Sequencing [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-0566-4554|https://orcid.org/0000-0003-0692-2105|https://frl.publisso.de/adhoc/uri/S2V0emVyLCBKdWxpdXM=|https://orcid.org/0000-0001-5767-7125|https://orcid.org/0000-0001-5773-5620|https://orcid.org/0000-0002-0352-2547|https://frl.publisso.de/adhoc/uri/WmltbWVybWFubiwgSsO8cmdlbg==|https://frl.publisso.de/adhoc/uri/R2ViYXVlciwgSnVkaXRo|https://frl.publisso.de/adhoc/uri/TWVyeiwgSGFydG11dA==|https://frl.publisso.de/adhoc/uri/QmVybmFyZCwgVmVyb25pY2E=|https://frl.publisso.de/adhoc/uri/SGFyZGVyLCBMYW5h|https://frl.publisso.de/adhoc/uri/UmF0amVuLCBLYXRoYXJpbmE=|https://frl.publisso.de/adhoc/uri/R2VzaywgU3RlZmFu|https://frl.publisso.de/adhoc/uri/UGV0ZXIsIFdvbGZnYW5n|https://frl.publisso.de/adhoc/uri/QnVzY2gsIFlhbm5paw==|https://frl.publisso.de/adhoc/uri/VHJvam9rLCBQZXRlcg==|https://orcid.org/0000-0001-9593-8947|https://frl.publisso.de/adhoc/uri/QmllcnNhY2ssIEhhcmFsZA==|https://frl.publisso.de/adhoc/uri/QnVzY2gsIEhhdWtl|https://frl.publisso.de/adhoc/uri/RmVsbGVyLCBBbGZyZWQgQy4=
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1000 Erstellt am 2023-04-27T09:58:34.330+0200
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