RB1 and osteosarcoma: Since a prior cell-cycle exit is required for immature osteosarcoma cells to undergo the terminal maturation that likely eliminates their tumorigenicity15, 16, and p53 and Rb pathways share the critical activity of restraining cell-cycle progression, defects in the p53 or/and Rb pathway(s) may confer dedifferentiation potential to osteosarcoma cells largely by reinstituting their entry into the cell cycle from the post-mitotic state17.