TP53 and osteosarcoma: In 1996, Miller CW.et al detected the mutations of TP53, RB1 and MDM2 genes in osteosarcoma by PCR-SSCP (single strand conformation polymorphism) [11], which genes were later proved to be the most frequently mutated genes in osteosarcoma, including TP53 and RB1 with the incidence of 31 − 82% and 19 − 64% in osteosarcoma respectively [12].