Not surprisingly, the loss of p53 function by mutation has been found in more than half of all human cancers and, unlike other tumour suppressors, the vast majority of TP53 mutations are missense mutations occurring within the DNA-binding domain of the protein resulting in a dominant-negative phenotype with a diminished ability to transactivate target genes e.g. the hot spot mutation R248W18. This evidence concerns the gene TP53 and neoplasm.