The first clues that murine osteosarcomagenesis can be driven by Rb1 and p53 pathway disruptions came in the high incidence of osteosarcomas in mice with transgenic expression of the SV40 large T antigen [49–52], which is known to bind and silence members of the Rb1 and p53 cell cycle checkpoint pathways, effectively disrupting them. This evidence concerns the gene TP53 and osteosarcoma.