Abstract Details

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

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S13 - Epilepsy/Clinical Neurophysiology (EEG) 1 (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

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 < 0.01.

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.

Authors/Disclosures
Anteneh M. Feyissa, MD, MSc, FAAN (Mayo Clinic) PRESENTER	Dr. Feyissa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurelis.
	No disclosure on file
	No disclosure on file
Mariet Allen, PhD (Mayo Clinic)	No disclosure on file
Nilufer Taner, MD, PhD, FAAN (Mayo Clinic)	The institution of Dr. Taner has received research support from NIH.
William O. Tatum IV, DO, FAAN (Mayo Clinic)	Dr. Tatum has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bioserenity. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Natus. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Defense Law Firm on behalf of a patient with epilepsy with funds donated to the Epilepsy Foundation of America. The institution of Dr. Tatum has received research support from Esai. The institution of Dr. Tatum has received research support from Mayo Clinic. The institution of Dr. Tatum has received research support from Liva Nova. The institution of Dr. Tatum has received research support from Engage Pharmaceuticals. The institution of Dr. Tatum has received research support from Xenon. Dr. Tatum has received intellectual property interests from a discovery or technology relating to health care. Dr. Tatum has received publishing royalties from a publication relating to health care. Dr. Tatum has received publishing royalties from a publication relating to health care. Dr. Tatum has received publishing royalties from a publication relating to health care. Dr. Tatum has a non-compensated relationship as a AAN Section Chair of Clinical Neurophysiology with AAN that is relevant to AAN interests or activities.
Steven S. Rosenfeld, MD, PhD (The Neurological Institute of New York)	No disclosure on file
	No disclosure on file
Alfredo Quinones-Hinojosa	Alfredo Quinones-Hinojosa has nothing to disclose.

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