CDK4 and osteosarcoma: Studies have documented that low-grade (parosteal and well-differentiated) osteosarcomas harbor a supernumerary ring and/or giant marker chromosomes with amplification of the 12q13–15 region, including the murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) genes, as well as subsequent overexpression of their respective proteins [21].