Abstract 358: Nf1 inactivation in NG2-cells is not sufficient for murine optic glioma formation.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Individuals with the tumor predisposition syndrome, neurofibromatosis 1 (NF1), are prone to development of low-grade astrocytomas (gliomas). These tumors frequently include optic pathway gliomas predominantly arising in young children. We have previously developed several Nf1 genetically-engineered mouse (GEM) strains that form optic gliomas similar to those that occur in children with NF1. However, in the optic nerve, there are two types of potential neuroglial progenitors, GFAP+ and NG2+ cells. This latter population has been shown to represent a potential cell of origin for rat malignant gliomas, suggesting that NG2+ progenitors may represent the initiating cell for Nf1 optic glioma. In this study, we employed a complementary series of in vitro and in vivo approaches to determine whether NG2+ cells could give rise to Nf1 optic glioma. First, we demonstrate that Nf1 loss in NG2+ cells does not increase glial cell proliferation in vitro. Second, NG2-Cre-expressing cells give rise to all three macroglial lineages (astrocytes, NG2+ cells, and oligodendrocytes) in vivo, similar to GFAP-Cre-expressing cells that drive Nf1 optic glioma formation. Third, in striking contrast to the GFAP-Cre strain, Nf1 loss in NG2+ progenitor cells in vivo is insufficient for optic gliomagenesis. Together, these data exclude NG2+ cells as the likely cell of origin for NF1-associated optic glioma and establish a model of gliomagenesis in which Nf1 loss occurs in specific neuroglial progenitors during embryonic development. Citation Format: Anne C. Solga, Scott M. Gianino, David H. Gutmann. Nf1 inactivation in NG2-cells is not sufficient for murine optic glioma formation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 358. doi:10.1158/1538-7445.AM2013-358