These next-generation sequencing studies have revealed underlying mechanisms, such as chromothripsis and kataegis, as well as a number of genes and pathways associated with osteosarcoma, especially those involved in genome maintenance (TP53, RB1, ATRX and homologous recombination) or hormonal signalling (IGF and ER signalling). This evidence concerns the gene RB1 and osteosarcoma.