Identification of biomarkers for predicting central nervous system involvement in patients with diffuse large B‐cell lymphoma

Introduction: Central Nervous System (CNS) involvement in Diffuse Large B Cell Lymphoma (DLBCL) is a rare complication associated with bad prognosis. The CNS Prognostic Index identifies patients high risk of relapse; however, its specificity limited and not accurate. Biomarkers that can predict relapse are still missing. For reason, we aimed to characterize the transcriptomic, genomic epigenomic hallmarks systemic tumors at diagnosis will CNS. Methods: We conducted retrospective study including 38 nodal DLBCL relapsed within first two years after diagnosis: 12 26 relapse. As controls, included 21 did DNA RNA were extracted from diagnosis. Immune infiltration was evaluated using nCounter PanCancer Profiling Panel (Nanostring); COO determined Lymph2Cx assay. Transcriptomic profiles generated by bulk sequencing; mutational analysis performed custom targeted NGS panel. Methylation described Illumina Infinium MethylationEPIC Array 850K (Figure 1A). Results: cell composition similar between groups; several genes overexpressed Genes related chemokine signaling as CCL14, IL7R, CCR6; adhesion like VCAM1 ITGA4; immune checkpoints BTLA upregulated group comparison without 1B). Among these, ITGA4 gene also found be when compared both no groups together 1C). No differences observed groups. Whole transcriptomic data showed enrichment genesets proliferation survival all others 1D). Patients had increased mutation load frequency PIM1, IGLL5 KMT2D genes. A total 343 CpG sites differentially methylated relapse, involving 211 1E). Keywords: Diagnostic Biomarkers, Extranodal non-Hodgkin lymphoma, Genomics, Epigenomics, Other -Omics conflicts interests pertinent abstract.