Analysis of Human Brain Tissue Transcriptome Reveals Risk Genes and Altered Molecular Pathways in Glioma-related Seizures (1044)

Objective: To identify novel pathways that lead to the development of glioma-related seizure (GRS) in patients. Background: Currently the exact mechanism and genetic alterations of GRS is poorly understood. Design/Methods: We collected transcriptome levels from: i) non-epiletic controls (n=5), ii) patients with GRS (n=9), iii) with glioma without seizures (non-GRS, n=8), and with iv) idiopathic temporal lobe epilepsy (iTLE, n=7) using an Illumina capture-based high-throughput RNA sequencing approach. Following sequence alignment and quality control, differential expression of gene (DEG) analysis was conducted. We identified molecular pathways enriched for DEG using Ingenuity Pathway Analysis. Significant expression of genes in each sample was defined with the log2 of the fold change at ≥ 2 and q-value Results: We identified 212 DEGs in the GRS vs. non-GRS analysis. Among these, 108 genes were up-regulated and 104 genes were down-regulated. There was significant up-regulation of genes involved in acute phase signaling and interaction pathways (NRK, MAPK15, and EFCAB1) and down-regulation of genes involved immune trafficking (CXLC8, CXCL6, and CCL20) in samples with GRS as compared to non-GRS samples. Compared to iTLE samples, there were 1015 DEGs in the GRS samples. Among these 877 genes were up-regulated and 138 genes were down-regulated in the GRS samples. There was significant enrichment for genes that have been previously shown to be markers of oncogenesis (EGFR, BRCA2, SOX4, TOP2A, and DLGAP5). Further, there was down-regulation of genes involved in solute carrier family (SLC5A5, SLC9A3, and SLC13A4) and glutamatergic neurotransmission (FOSB and vesicular glutamate transporter-2) in the GRS samples. Conclusions: Our findings suggest that alterations in acute phase signaling, inflammation-related processes, and glutamatergic neurotransmission may underlie GRS. Further, there may be distinct mechanisms of seizure genesis in GRS vs. iTLE. Our findings require replication in larger human cohorts and functional experiments to explore the function of the genes perturbed in GRS. Disclosure: Dr. Feyissa has nothing to disclose. Dr. Carrano has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Allen has nothing to disclose. Dr. Taner has nothing to disclose. Dr. Tatum has received personal compensation in an editorial capacity for Elsevier. Dr. Tatum has received royalty, license fees, or contractual rights payments from Demos Medical Publishing, LLC. Dr. Rosenfeld has nothing to disclose. Dr. Guerrero Cazares has nothing to disclose. Dr. Quinones-Hinojosa has nothing to disclose.