TP53 and Li-Fraumeni syndrome: GOF in p53 is supported by evidence that mice expressing p53 R172H or R270H mutants (equivalent to human R175H and R273H) develop a greater number of metastatic tumors than p53−/− mice [60,61], and by the observation that patients with Li-Fraumeni syndrome carrying p53 missense mutations are characterized by earlier tumor development, than patients with a p53 deletion [62].