PM-12 * Pax3 EXPRESSION ENHANCES PDGF-B-INDUCED BRAINSTEM GLIOMAGENESIS AND CHARACTERIZES A SUBSET OF BRAINSTEM GLIOMA

High-grade Brainstem glioma (BSG), also known as Diffuse Intrinsic Pontine Glioma (DIPG), is an incurable pediatric brain cancer. Increasing evidence supports the existence of regional differences in gliomagenesis such that BSG is thought to be a distinct disease from glioma of the cerebral cortex (CG). In an effort to elucidate unique characteristics of BSG, we conducted expression analysis of mouse PDGF-B-driven BSG and CG initiated in Nestin progenitor cells and identified a short list of expression changes specific to the brainstem gliomagenesis process, including upregulation of paired box 3 (Pax3). In the neonatal mouse brain, while Pax3 expression is absent from the cerebral cortex, its expression marks a subset of brainstem progenitor cells, mirroring its regional expression in glioma. Ectopic expression of Pax3 in normal brainstem progenitors in vitro shows that Pax3 inhibits apoptosis. In vivo, Pax3 enhances PDGF-B-driven gliomagenesis by significantly shortening tumor latency (p = 0.02 by log rank test), and increasing tumor penetrance (from 25% to 80%, p = 0.0003 by Fisher's exact test), in a region-specific manner, while loss of Pax3 function in PDGF-B-driven;p53-deficient BSG significantly delays glioma formation (median survival of 38 versus 28.5 days, p = 0.0007 by log rank test). Importantly, Pax3 is regionally expressed in human glioma as well, with high PAX3 mRNA characterizing 40% of human BSG, revealing a subset of tumors that significantly associates wit...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: PRECLINICAL TUMOR/ANIMAL MODELS Source Type: research