Transcriptional profiling of EGFR variants in mouse Glioblastoma model. Transcriptional profiling of EGFR variants in mouse Glioblastoma model

The RTK/PI3K/MAPK pathway is one of the most frequently altered pathways in Glioblastoma (GBM) with EGFR mutations and/or amplifications present in 57% of all samples. It remains the most frequently mutated oncogene in GBM. We utilized an established in vivo competition screening assay to identify and validate bona fide, driver mutations in GBM. The screen nominated A298I, T263P, and R108G mutations as potential drivers. We also analyzed R108K and R222C which were not identified by the screen. The goal of this study is to characterize the transcriptional changes of GBM when driven by different EGFR variants. Using in utero electroporation (IUE) and CRISPR/Cas9 constructs we knocked out Tp53 and Pten in developing glial cells. Each EGFR variant was overexpressed in this model and tumors were collected at end stage for RNA-sequencing analysis. Overall design: Bulk tumor was collected from 3-5 mice for each variant on post-natal day 70 and the effect of EGFR variants on GBM was determined through RNA-seq transcriptomic profiling.