Deep Multiple-omics Profiling of Brain Tumors Identifies Signaling Networks Downstream of Cancer Driver Genes

We profiled the transcriptome in two high-grade glioma (HGG) mouse models driven by mutated receptor tyrosine kinase (RTK) oncogenes, platelet-derived growth factor receptor alpha (PDGFRA), neurotrophic receptor tyrosine kinase 1 (NTRK1). In addition, transcriptome for normal mouse cortex was also profiled. The transcriptome was used to define transcription factor activity by integrating with whole proteome and phosphoproteome datasets. Overall design: 7 samples with PDGFRA Mutant, 7 samples with TPM3-NTRK1 fusions, 4 normal mouse cortex samples; [1] A pooled population of p53-deficient primary mouse astrocytes was transduced with retrovirus expressing human PDGFRA D842V mutation along with an IRES-GFP. 2 × 10^6 cells per mouse were intracranially implanted into athymic nude mice [2] A pooled population of p53-deficient primary mouse astrocytes was transduced with retrovirus expressing human TPM3-NTRK1 fusion along with an IRES-GFP. 2 × 10^6 cells per mouse were intracranially implanted into athymic nude mice [3] Normal brain cortex of athymic nude mice