Abstract IA07: The effect of cell of origin on GBM phenotype

Abstract

Abstract Current thinking about solid tumor biology is largely influenced by analysis of the large data sets afforded by modern genomic capabilities. In GBM, classification of tumors into four categories (proneural, neural, mesenchymal, and classic) relies on differential transcriptional profiles coupled with copy numbers, and mutational profiles. These approaches for example, imply EGFR receptor as a major driver of Classic sub-type whereas NF1 mutations are preferentially found in mesenchymal subtypes. Functional evidence that these molecular categories indeed reflect biologically different tumors remains to be proved. We have generated mouse models of GBM by driving loss of function of in the NF1, p53 and Pten tumor suppressors. We find that two phenotypically and biologically different GBMs emerge that reflect tumor initiation different adult CNS progenitor populations. Thus, in a mouse model, distinct progenitor cell populations dictate different tumors created by mutation in identical drivers. Citation Format: Luis F. Parada. The effect of cell of origin on GBM phenotype. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr IA07.