A new mechanism termed loss-translocation-amplification (LTA) chromothripsis that has been described in approximately 50% of high-grade osteosarcomas in which two pathways converge to simultaneously inactivate TP53, and amplify multiple oncogenes through successive break-fusion-bridge cycles, makes osteosarcoma represent very complex chromosomal rearrangements in human cancer. Here, TP53 is linked to osteosarcoma.