It was reported that RB is needed to promote the osteogenic differentiation program of mesenchymal stem/stromal cells (MSCs) [16] and, therefore, it could be speculated that RB mutations synergize with P53 inactivation in OS formation only when mutations occur in osteogenic-committed cell types; meanwhile it could favor other sarcoma phenotypes when mutated in more immature cell types (see below). The gene discussed is TP53; the disease is sarcoma.