Abstracts

Gangliogliomas are mixed glial-neuronal tumors with a predilection for epileptogenesis. Unlike higher grade infiltrating gliomas, these low-grade tumors generally have discrete margins. Resection of gangliogliomas may result in decreased seizure incidence, suggesting that the focus of epileptogenicity lies within the tumor itself. In cases where resection fails to achieve seizure reduction, adjacent cortex may also provide a seizure focus.
Comparison of gene expression between ganglioglioma neurons, and neurons from the adjacent cortex provides insight into the mechanisms of epileptogenesis. We performed in situ RNA transcription on sectioned pathology specimens from patients who had undergone partial lobectomy for seizure-inducing gangliogliomas in the temporal lobe. Patient outcomes at a mean of four years after resection ranged from Engels 1A (completely seizure-free), to 3A (worthwhile reduction in seizures). Individual neurons were microdissected from the tumors and their adjacent cortex. Amplified single cell RNA was radiolabelled, and hybridized to lab-generated cDNA arrays for analysis of gene expression which was performed using JMP statistical software. Comparisons of gene expression between ganglioglioma neurons and neurons from adjacent temporal cortex revealed differential expression of inhibitory (GABA[sub]A[/sub])and excitatory (NMDA/GluR) neurotransmitter and receptor subunits. Expression of proinflammatory cytokines, growth factors, growth factor receptors, signal transducers and transcription factor mRNAs were distinct between these cell populations. Analysis of gene expression in neurons microdissected from ganglioglioma and its adjacent cortex provides insight into the mechanisms by which these tumors cause seizures. (Supported by NINDS RO1NS04542 and R21NS39928.)