Single B-Cell Genomic Analyses Differentiate Vitreoretinal Lymphoma from Chronic Inflammation.
Ophthalmology
; 128(7): 1079-1090, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-33221324
ABSTRACT
PURPOSE:
To test whether analyzing DEPArray (Menarini Silicon Biosystems) isolated single B cells from the vitreous fluid can reveal crucial genomic and clinicopathological features to distinguish patients with vitreoretinal lymphoma (VRL) from those with chronic inflammation using immunoglobulin heavy chain (IGH), disease biomarker myeloid differentiation primary response 88 (MYD88)L265P mutation, and copy number profiling.DESIGN:
A single-center, retrospective study.PARTICIPANTS:
Remnant vitreous biopsies from 7 patients with VRL and 4 patients with chronic inflammation were acquired for molecular analysis.METHODS:
Vitreous fluid samples were prefixed in PreservCyt (Hologic) and underwent cytologic analysis and immunohistochemistry examination. Single cells were isolated using the DEPArray NxT system, followed by downstream genomic analysis. MAIN OUTCOMEMEASURES:
The frequencies of the dominant IGH and MYD88L265P mutation and the genome-wide copy number aberration (CNA) profiles of individual vitreous-isolated B cells were characterized.RESULTS:
An average of 10 to 13 vitreous B cells were used in the single-cell IGH and MYD88 analyses. Higher frequencies of dominant IGH (88.8% ± 13.2%) and MYD88L265P mutations (35.0% ± 31.3%) were detected in patients with VRL than in patients with chronic inflammation (65.9% ± 13.4% and 1.5% ± 2.6% for IGH and MYD88L265P, respectively). In a cytology-proven VRL case, all 15 vitreous isolated B cells were derived from the same clone with 100% paired IGH immunoglobulin light chain (IGK) sequences. Genome-wide copy number profiling revealed a high degree of similarity between B cells from the same patient with VRL, with extensive gains and losses at the same areas across the whole genome. In addition, 14 of 15 B cells showed a BCL2/JH t(14;18) translocation, confirming cellular malignancy with a clonal origin. Clustering analysis of the copy number profiles revealed that malignant B cells derived from different patients with VRL had no common genome-wide signatures.CONCLUSIONS:
Single B-cell genomic characterization of the IGH, MYD88L265P mutation, and copy number profile enables VRL diagnosis. Because our study involved only a small cohort, these meaningful proof-of-concept data now warrant further investigation in a larger patient cohort.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retina
/
Linfócitos B
/
Linfoma Difuso de Grandes Células B
/
Neoplasias da Retina
/
Fator 88 de Diferenciação Mieloide
/
Inflamação
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Ophthalmology
Ano de publicação:
2021
Tipo de documento:
Article