TP53 and hereditary disease: Although the spectrum of the TP53 missense mutations is vast – counting about 1,800 different amino-acid changes (8) – several hotspot p53 mutants, in particular, affecting residues R273, R248, R175, and G245 of the p53 protein, are present with a higher frequency both in sporadic tumors (together over 21% of total missense mutations) and in individuals with the Li–Fraumeni syndrome (LFS), a genetic disorder caused by inherited TP53 mutations that predispose carriers to an early-onset development of various cancers (9).