CDKN2A and Li-Fraumeni syndrome: They frequently have TP53 and RB1 mutations34, 39 and alterations affecting cell cycle checkpoints, such as reduced p16INK4A expression.40 Patients with Li-Fraumeni syndrome and hereditary retinoblastoma are predisposed to develop osteosarcomas.41, 42 Disruption of p53 often leads to genomic instability, defective nocodazole-induced mitotic spindle checkpoints and resistance to radiation, all of which we observed.