Given the highly treatment-resistant nature of GBM, studies from The Cancer Genome Atlas (TCGA) and Parsons et al. first dissected the mutational landscape of GBM with the aim of discovering actionable mutations or predictive signatures.3,4 With over 200 GBM samples characterized through DNA copy number, gene expression, and DNA methylation profiling, TCGA was able to identify three critical signaling networks that harbor the most frequent mutations: Receptor tyrosine kinase (RTK) signaling, p53 signaling, and RB signaling. The gene discussed is RB1; the disease is glioblastoma.