The Genetic Profile of Large B-Cell Lymphomas Presenting in the Ocular Adnexa

Stine Dahl Vest, Patrick Rene Gerhard Eriksen, Fleur A. de Groot, Ruben A.L. de Groen, Anne H.R. Kleij, Marina Knudsen Kirkegaard, Peter Kamper, Peter Kristian Rasmussen, Christian von Buchwald, Peter de Nully Brown, Jens Folke Kiilgaard, Joost S.P. Vermaat, Steffen Heegaard*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL) presenting in the ocular adnexa. Pathogenic variants and copy number variations in 128 B-cell lymphoma-relevant genes were analyzed by targeted next-generation sequencing. Genetic subtypes were determined with the LymphGen algorithm. Primary ocular adnexal DLBCL-NOS constituted 50% (n = 14) and was generally characterized by non-germinal center B-cell origin (non-GCB) (n = 8, 57%), and LymphGen MCD subtype (n = 5, 36%). Primary ocular adnexal DLBCL-NOS presented pathogenic variants in genes involved in NF-κB activation and genes which are recurrently mutated in other extranodal lymphomas of non-GCB origin, including MYD88 (n = 4, 29%), CD79B (n = 3, 21%), PIM1 (n = 3, 21%), and TBL1XR1 (n = 3, 21%). Relapsed DLBCL-NOS presenting in the ocular adnexa (n = 6) were all of non-GCB origin and frequently of MCD subtype (n = 3, 50%), presenting with a similar genetic profile as primary ocular adnexal DLBCL-NOS. These results provide valuable insights into genetic drivers in ocular adnexal DLBCL-NOS, offering potential applications in future precision medicine.

Original languageEnglish
Article number3094
JournalInternational Journal of Molecular Sciences
Volume25
Issue number6
ISSN1661-6596
DOIs
Publication statusPublished - Mar 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

  • copy number variation
  • diffuse large B-cell lymphoma
  • genetics
  • high-grade B-cell lymphoma
  • mutation
  • next-generation sequencing
  • ocular adnexal lymphoma

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