Genomic and transcriptomic profiling identifies aberrant signalling pathways in ocular B cell lymphoma

Abstract

Purpose : Ocular adnexal B cell lymphoma (OABL) is a rare extra-nodal malignancy that manifests as different molecular subtypes. Despite the advent of treatment modalities, disease recurrence is a major challenge in treating OABL patients. Disease presentation at an older age, disseminated lymphoma and poor differentiation are the predictors of poor disease outcomes. However, the molecular characteristics determining disease outcomes are poorly understood. Thus, we aim to understand the molecular drivers involved in the pathogenesis of OABL through integrated OMICS.

Methods : Whole exome (n=11) and RNA sequencing (n=9) were performed in primary tumors of OABL. For exome data, GATK was used for variant calling and the pathogenic variants were prioritized using functional predicted scores to dissect the cancer-predisposing somatic events. From RNA Sequencing, differentially expressed genes (DEGs) were identified by DESeq2 (R-Package). Further, dysregulated pathways were predicted by Gene Ontology and KEGG pathway enrichment analyses.

Results : Whole exome sequencing uncovered pathogenic mutations in hallmark genes including MYD88(18%), CD79b(18%), KMT2C(36%), PIK3R1(18%) and CDC27(63%). Interestingly, most of the pathogenic variants were enriched in NFkB, PI3K and B-Cell Receptor signalling pathways. Gene ontology analyses of DEGs revealed alterations in PI3K, NFkB signalling, focal adhesion, ECM receptor interaction and receptor tyrosine kinase pathways. Besides, the molecular activity of immune receptors involved in the immune response was profoundly affected.

Conclusions : PI3K & NFkB signalling pathways were concordantly dysregulated at the genomic and transcriptomic levels. This comprehensive finding lays the groundwork for understanding the molecular signatures in OABL progression. Further analyses will lead to develop reliable prognostic markers in OABL.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Aberrant signalling landscape in OABL tumors revealed by gene ontology analysis