The increase in short to FL transcript ratio in osteosarcomas correlates with reduced MDMX protein levels, faster metastatic progression and greatly reduced patient survival.20 Lower MDMX protein levels in many osteosarcoma or breast cancer cell lines and in soft tissue sarcomas correlate with compromised p53 function.20 Although it is likely that p53-mutant tumor cells have lost the selective pressure to maintain high levels of functional MDMX, it is unclear why loss of functional MDMX in these cells correlates with a more aggressive cancer. This evidence concerns the gene MDM4 and osteosarcoma.