298 Differential Gene Expression Underlying Glioma Related Epilepsy

Abstract

INTRODUCTION: Seizures are a common sequalae for patients suffering from gliomas. There are several factors, such as molecular characteristics, known to influence the initiation of seizures that may ultimately drive tumor growth. However, different levels of gene expression associated with seizures for gliomas remain unclear. Here, we review current literature and analyze RNA sequencing of gliomas to further probe these differences. METHODS: Utilizing total RNA sequencing obtained from The Cancer Genome Atlas - Lower Grade Glioma to identify and characterize differential expression in patients that do and do not experience seizures. Utilizing QIAGEN Ingenuity Pathways Analysis (IPA), we identified canonical and functional pathways to further characterize differential expression. RESULTS: From 289 patients with gliomas, 83 (28.7%) had available information regarding seizures and other variables of interest. Of these, 50 (60.2%) were allocated to the seizure group and the remaining 33 (39.8%) to the non-seizure group. There were no statistically significant differences in age (p = 0.4661), sex (p = -0.1338), race/ethnicity (p = 0.7331), molecular subtype (0.8656), tumor grade (p = 0.2260), or anatomical location. When comparing the level of RNA expression from these tumors between the seizure and non-seizure groups, we identified 52 genes that were significantly differentially regulated. Critical canonical pathways were identified, most significantly RHOGDI and Semaphorin Neuronal Repulsive signaling.Finally, in the functional analysis, tumors that promoted seizures had gene sets that were significantly increased involving neuronal differentiation and synaptogenesis. CONCLUSIONS: In the setting of gliomas, differences in tumor gene expression exist between individuals with seizures and without seizures despite similarities in patient demographics and other tumor characteristics. There was significant difference in gene expression that were most associated with neuron development and synaptogenesis, ultimately suggesting a mechanistic role of a tumor-neuron synapse in seizure initiation and potentially tumor growth.