Abstracts

Rationale: Tumor associated seizures (TAS) are common and debilitating and is likely multifactorial. Recently, dysregulation of extracellular glutamate through the transporter system xc- has been shown to be a critical mechanism in TAS. This transporter is encoded by the gene SLC7A11. It is unknown whether SLC7A11 is differentially expressed in gliomas, and whether the influence of SLC7A11 has any regional variability, i.e. that it is associated with TAS in only certain brain regions. To address these questions, we harnessed the gene expression and MRI data of adult glioblastomas from two large public repositories: The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA). We hypothesize that SLC7A11 expression is greater in patients with TAS, and that the gene expression is most significant over the temporal lobe. Methods: We analyzed a cohort of 60 patients with newly diagnosed glioblastomas from TCGA in whom TAS information was obtained. Patients were classified as presenting with or without TAS. Gene expression of SLC7A11 was obtained by a Level 2 inquiry. MR images were transformed into a standardized stereotaxic coordinate space based on the Talairach atlas and tumors were segmented. To increase power, all right hemispheric tumors were flipped across the midline to the left. To assess the localizing value of the tumors causing seizures, a T- statistic map was calculated. For each patient, the entire tumor mask was assigned the gene expression value associated with that patient. At each voxel, the T-statistic of the gene expression difference between patients with and without TAS was calculated. To assess the areas of significance of the resulting T-statistic map, a non-parametric mapping method based on permutation of the signal clusters were obtained. Clusters of the that exceeded significance of p<0.05 were considered significant. Results: Of 60 patients, 17 presented with TAS. Four of the patients had IDH1 mutations and were excluded from analysis. Patients with TAS had smaller tumor volumes (32.4 vs 48.4 cubic cc, p<0.05). Groupwise analysis revealed that SLC7A11 expression was higher in patients with TAS (mean 30.35 vs 28.17, p=0.045). The significance map (Figure) reveals a region in the temporal lobe where SLC7A11 expression was significantly higher in patients with TAS. Conclusions: We demonstrated increased SLC7A11 expression in patients with TAS. Furthermore, SLC7A11 expression revealed highest correlation to TAS in the temporal lobe. As a result, we hypothesize that anti-glutaminergic treatments are potentially most effective in temporal, rather than frontal or midline, tumors.