TP53 and cancer: i) somatic mutations of p53 detected in various cancers showed a highly significant excess of non-synonymous over synonymous substitutions, which is the signature of positive selection[27], ii) amino acid replacements caused by cancer-associated mutations clustered within evolutionarily conserved, functionally important regions of p53, and iii) mutational hotspots, the sites of frequent mutation which are subject to particularly strong positive selection, differed depending on the type of tumor, which suggests acquisition of distinct new functions by p53 in different tumors.