High throughput proteomics profiling provide an unprecedented opportunity for dissecting molecular mechanisms in cancer biology. Here we present deep profiling of whole proteome and phosphoproteome in two high-grade glioma mouse models driven by mutated receptor tyrosine kinase (RTK) oncogenes. Using multiplex isobaric labeling (10-plex TMT) coupled with extensive liquid chromatography and mass spectrometry, we analyzed ~ 12K genes and > 30K phosphosites by extensive mass spectrometry. Systematical reprogramming of the proteome and phosphoproteome were observed in HGG tumors compare to normal cortex.