MDM4 and osteosarcoma: MDM gene amplification and/or overexpression have been observed in a variety of human cancers, including leukemia and lymphoma, breast cancer, glioblastoma, soft tissue sarcoma, osteosarcoma and retinoblastoma.9, 10, 11 As most tumors with amplified copy numbers of MDM genes retain wild-type p53,10, 12 the increased level of MDM2 or MDMX proteins is thought to promote oncogenesis by inhibiting p53 activity in these cells.