Characterization of a novel pdgf-a driven in vitro model of high-grade glioma

Abstract

Glioblastoma (GBM) is a fatal cancer, thought to arise from astrocytes or precursors, including oligodendrocyte progenitor cells (OPCs). Although many of the key molecular alterations in GBM including p53 mutation and amplification of platelet derived growth factor receptor-alpha (PDGFR-a) are known, our understanding of this disease remains incomplete. Here, we show that cells from the subventricular zone of p53-/- mice growing m PDGF-A, transform giving rise to a population of cells that proliferate continuously in the absence of exogenous PDGF-A. When grafted into the brains of immunocompetent mice, they form cellular, invasive GBM-like tumors. This population of cells expresses PDGFR-a and Olig2, OPC markers. Thus, a subpopulation of PDGFR­a positive OPCs in the SVZ of adult p53-/- mice transform in the presence of PDGF-A. This model might be used to identify other molecular events that occur in secondary GBM, where early p53 and PDGFR-a alterations are signature genetic changes.