Tumor associated seizures in glioblastomas are influenced by survival gene expression in a region-specific manner: A gene expression imaging study

Abstract

Tumor associated seizures (TAS) are common and cause significant morbidity. Both imaging and gene expression features play significant roles in determining TAS, with strong interactions between them. We describe gene expression imaging tools which allow mapping of brain regions where gene expression has significant influence on TAS, and apply these methods to study 77 patients who underwent surgical evaluation for supratentorial glioblastomas. Tumor size and location were measured from MRI scans. A 9-set gene expression profile predicting long-term survivors was obtained from RNA derived from formalin-fixed paraffin embedded tissue. A total of 32 patients (42%) experienced preoperative TAS. Tumor volume was smaller (31.1 vs 58.8 cubic cm, p<0.001) and there was a trend toward median survival being higher (48.4 vs 32.7 months, p = 0.055) in patients with TAS. Although the expression of only OLIG2 was significantly lower in patients with TAS in a groupwise analysis, gene expression imaging analysis revealed regions with significantly lower expression of OLIG2 and RTN1 in patients with TAS. Gene expression imaging is a powerful technique that demonstrates that the influence of gene expression on TAS is highly region specific. Regional variability should be evaluated with any genomic or molecular markers of solid brain lesions.

Seizure‐susceptible brain regions in glioblastoma: identification of patients at risk

“…In our cohort, there were no significant differences regarding tumoral GM or WM involvement between the groups. In brief, all of these findings support the fact that tumor location plays an important role in developing seizures in GBM .…”

“…Previous studies proposed that glial tumors located in frontal, parietal, insular and temporal lobes were more epileptogenic . However, most of these studies did not use a volumetric imaging analysis for precise localization of seizure‐related regions.…”

“…These results were externally validated visually and automatically, exhibiting, mostly with the automatic method, high PPV and NPV. Previous studies proposed that glial tumors located in frontal, parietal, insular and temporal lobes were more epileptogenic [2,15]. However, most of these studies did not use a volumetric imaging analysis for precise localization of seizure-related regions.…”

Epilepsy in Adults with Supratentorial Glioblastoma: Incidence and Influence Factors and Prophylaxis in 184 Patients

“…This may be due to an epileptic susceptibility or gene that may have played a role in epileptogenesis, as has been previously suggested. [ 1 , 6 – 7 ]…”

Epilepsy Associates with Decreased HIF-1α/STAT5b Signaling in Glioblastoma

“…We have shown that such mutations cannot solely explain the favorable prognosis of epileptogenic glioblastomas [7]. A lower expression of OLIG2 , linked to the proneural GBM subtype [3], was also related to an increased risk of tumor-associated seizures [19]. How this could relate to the prognosis is however unknown.…”