The molecular hallmarks of primary and secondary vitreoretinal lymphoma

Bonzheim, Irina, Sander, Philip, Salmeron-Villalobos, Julia, Suesskind, Daniela, Szurman, Peter, Gekeler, Florian, Spitzer, Martin S, Steinhilber, Julia, Kohler, Esther, Buessgen, Melanie
et al (show 6 more authors) (2022) The molecular hallmarks of primary and secondary vitreoretinal lymphoma. BLOOD ADVANCES, 6 (5). pp. 1598-1607.

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Vitreoretinal lymphoma (VRL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) considered a variant of primary central nervous system lymphoma (PCNSL). The diagnosis of VRL requires examination of vitreous fluid, but cytologic differentiation from uveitis remains difficult. Because of its rarity and the difficulty in obtaining diagnostic material, little is known about the genetic profile of VRL. The purpose of our study was to investigate the mutational profile of a large series of primary and secondary VRL. Targeted next-generation sequencing using a custom panel containing the most frequent mutations in PCNSL was performed on 34 vitrectomy samples from 31 patients with VRL and negative controls with uveitis. In a subset of cases, genome-wide copy number alterations (CNAs) were assessed using the OncoScan platform. Mutations in MYD88 (74%), PIM1 (71%), CD79B (55%), IGLL5 (52%), TBL1XR1 (48%), ETV6 (45%), and 9p21/CDKN2A deletions (75%) were the most common alterations, with similar frequencies in primary (n = 16), synchronous (n = 3), or secondary (n = 12) VRL. This mutational spectrum is similar to MYD88mut/CD79Bmut (MCD or cluster 5) DLBCL with activation of Toll-like and B-cell receptor pathways and CDKN2A loss, confirming their close relationship. OncoScan analysis demonstrated a high number of CNAs (mean 18.6 per case). Negative controls lacked mutations or CNAs. Using cell-free DNA of vitreous fluid supernatant, mutations present in cellular DNA were reliably detected in all cases examined. Mutational analysis is a highly sensitive and specific tool for the diagnosis of VRL and can also be applied successfully to cell-free DNA derived from the vitreous.

Item Type: Article
Uncontrolled Keywords: Vitreous Body, Humans, Lymphoma, Non-Hodgkin, Retinal Neoplasms, Central Nervous System Neoplasms, Uveitis, Lymphoma, Large B-Cell, Diffuse, Cell-Free Nucleic Acids
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 24 Mar 2023 12:44
Last Modified: 24 Mar 2023 12:44
DOI: 10.1182/bloodadvances.2021004212
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