Given that Rb is known to drive withdrawal from the cell cycle upon differentiation of many cell types (10–14), we hypothesize that abrogation of Rb and compensatory proteins p107 and p130 (collectively responsible for tumor suppression in murine astrocytes) initiates GBM in differentiated astrocytes by inducing a progenitor phenotype, thus generating a highly proliferative cell population with sensitivity to drivers of progression. This evidence concerns the gene RB1 and neoplasm.