The dedifferentiation process essentially underlies the genesis of osteosarcoma that is marked with mesenchymal immaturity, as the targeted-deletion of p53 or both p53 and Rb in committed or mature osteoblasts rather than in mesenchymal stem cells (MSCs) results in osteosarcoma in mouse models4, 11, 12, 13. Here, RB1 is linked to osteosarcoma.