The molecular hallmarks of primary and secondary vitreoretinal lymphoma
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ABSTRACT:
PROVIDER: PRJEB42294 | ENA |
REPOSITORIES: ENA
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Project description:Vitreoretinal lymphoma is a rare subtype of diffuse large B-cell lymphoma considered a variant of primary central nervous system lymphoma. Its diagnosis requires examination of vitreous fluid, but cytologic differentiation from uveitis remains difficult. Due to its rarity and difficulty in obtaining diagnostic material, little is known about the genetic profile of the disease.
2022-07-19 | GSE164910 | GEO
Project description:The molecular hallmarks of primary and secondary vitreoretinal lymphoma
| PRJNA692437 | ENA
Project description: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.
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Project description:Follicular lymphoma (FL) is characterized by the t(14;18)(q32;q21), frequent numerical chromosomal alterations, and recurrent somatic mutations. However, no genetic studies are available for FL in situ (FLIS), a putative precursor lesion of FL. In this study, we analyzed cases of FLIS without manifest (m)FL, partial involvement by FL (PFL), and paired cases of FLIS and mFL to detect possible early chromosomal imbalances, as well as DNA-methylation patterns of genomic regions of selected genes. We demonstrated that paired FLIS and mFL cases are always clonally related. FLIS and PFL have no or few secondary chromosomal imbalances detectable by copy number arrays and a lower level of gene methylation as compared to mFL. Additionally, EZH2 Tyr641 mutations were detected in a subset of both FLIS and PFL cases. In conclusion, this study provides evidence that FLIS represents a FL precursor lesion of long-lived clonal B-cells carrying the t(14;18) with no or few secondary genetic changes. The earliest secondary genetic alterations detected in FLIS are the EZH2 Tyr641 mutation and low levels of CNAs, as evidence of clonal evolution. Our data suggest that there may be more than one distinct lesion driving the progression from FLIS to manifest lymphoma.
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