New candidate gene mutation in astrocytoma with seizures

Patients with astrocytomas frequently experience seizures. Patients with glioma who had preoperative epilepsy had significantly longer survival than those without seizures. However, the preoperative risk factors for seizures remain unclear. Moreover, previous studies have suggested that tumor genomics, rather than tumor location, mass effect, or tumor volume, plays a critical role in seizures in glioma. This study aimed to investigate the somatic genomic landscape of astrocytomas and its association with seizure occurrence. Baseline clinical characteristics, including MRI findings, did not differ between patients with astrocytoma presenting with or without seizures. Analysis of exome sequences from 40 samples revealed 22,891 single-nucleotide variants and 1,801 insertions or deletions. The top five cancer-related genes identified in our cohort were TP53, IDH1, ATRX, NOTCH1, and EGFR, detected in 48%, 28%, 25%, 25%, and 25% of cases, respectively. The top five most common driver genes were MUC16, TP53, MUC4, HLA-A, and IDH1. Seizure events in patients with astrocytoma were significantly associated with variants in nine genes. We identified two novel mutated genes, GSTT4 and CELSR1, that were significantly more prevalent in the seizure group. Future research should expand the cohort and conduct a functional analysis of GSTT4 and CELSR1 to identify new treatment targets and provide additional evidence to guide clinical decision-making.