LG-73: CHARACTERIZATION OF GANGLIOGLIOMA AS A NEURODEVELOPMENTAL DISORDER

INTRODUCTION: Gangliogliomas (GG) are low-grade, well differentiated neuroepithelial tumours of the central nervous system (CNS) comprised of neoplastic glial and neuronal cells. From microarray data, gangliogliomas overexpress the homeobox gene DLX2 required for differentiation and migration of inhibitory interneurons in the embryonic forebrain. We are interested in the role DLX2 plays in specifying neural progenitor fate. We hypothesize that in CNS progenitors, DLX2 regulates neural versus glial cell fate decisions. METHODS: DLX2 expression was examined in a cohort of ganglioglioma FFPE sections using immunohistochemistry and dual immunofluorescence labelling. Co-localization of DLX2 with glial fibrillary acidic protein (GFAP; glial marker) and synaptophysin (neural marker) was carried out. BRAF V600E mutation status was also assessed. RESULTS: In our discovery cohort of 30 patient samples (Instituto Giannina Gaslini), 10 samples expressed DLX2. In our validation cohort of 42 patients (University of Alberta), 6 of 12 tumours examined so far have the V600E mutation. One heavily pretreated patient with progressive cervicomedullary disease has had a very good partial response to BRAF inhibitor therapy. 16 of 26 samples studied to date expressed nuclear DLX2. All 16 DLX2(+) tumours co-expressed GFAP and synaptophysin. CONCLUSIONS: Our results support that GG arise from bipotential CNS progenitors arrested at the neuronal-glial cell fate “decision” point. As an alternative to offering adjunct therapy using chemotherapy and/or radiation for recurrent/progressive disease, biological or differentiation-based treatments could be considered +/- BRAF inhibitors for those GG with or without the V600E mutation, respectively. Correlation of BRAF mutational status and DLX2 expression is in progress.