Next Generation Sequencing Mutational Profiles of Gliomas Presenting With and Without Seizure

INTRODUCTION: Seizures are among the most common presentation of gliomas in adults, but much remains unknown regarding the relationship between underlying tumor biology and epileptic activity. METHODS: We conducted a single-center retrospective review of 140 adult patients who underwent surgical management of glioma with next generation sequencing of tumor samples obtained 2016-2020. Univariate odds ratios were computed for relevant cohort characteristics. RESULTS: Among patients with documented seizure history, 71 (51.1%) presented with seizures while 68 (48.9%) did not. At time of diagnosis, patients presenting with seizure were younger (47 vs 60.5, p = 0.0001) and had more recurrent disease (60.6% vs 16.7%, p < 0.0001). Patients presenting with seizure had fewer glioblastomas (OR: 0.2 [0.09-0.41], p < 0.0001) but more astrocytomas (OR: 4.78 [1.68-13.65], p = 0.0038) and oligodendrogliomas (OR: 3.47 [1.07-11.27], p = 0.0557). Of the top 15 most common mutations in our cohort, patients presenting with seizure had fewer instances of IDH1 (OR: 5.26 [2.44-11.32], p<0.0001), polysomy 7/monosomy 10 (OR: 0.48 [0.24-0.95], p = 0.0523), and PTEN mutation (OR: 0.46 [0.22-0.98], p = 0.0646), but more instances of 1p/19q codeletion (OR: 3.47[1.07-11.27], p = 0.0557), ATRX (OR: 2.54 [1.15-5.59], p = 0.0315) and CIC (OR: 13.63 [1.72-107.97], p = 0.0046) mutations. Notably, mutations in NF1 (OR: 0.73 [0.28-1.88)], p = 0.6753), TP53 (OR: 1.1 [0.56-2.15], p = 0.9194), TERT (OR: 0.63 [0.31-1.28], p = 0.2679), CDKN2A/B (OR: 0.61 [0.31-1.21], p = 0.2154), and EGFR (OR: 0.49 [0.21-1.13], p = 0.1396) were not associated with seizure presentation. CONCLUSIONS: ATRX and CIC mutations are positively associated with seizure presentation while polysomy 7/monosomy 10 and PTEN mutations are negatively associated. Future analysis of this cohort is needed to better characterize the influence of tumor mutational profile on preoperative as well as postoperative seizure activity.