TP53 and neoplasm: Li-Fraumeni patients carry a germline p53 mutation in one allele compromising the function of p53.80, 81, 82 Different studies have reported that preosteoblasts and osteoblasts represent the cells of origin of OS.78, 83 Importantly, cellular microenvironment is also decisive in determining the fate of stem cells and in promoting tumor formation.84 The osteogenic differentiation of p53-deficient or mutant MSCs can be affected by signals from BME and promote eventually OS.