Hypermutability and silent mutations in human carcinogenesis

Silent or synonymous mutations are nucleotide changes which do not result in an amino acid change. Such alterations make up approximately 4% of the total TP53 mutations in a database of almost 10,000 mutations. Insofar as these changes do not confer a selective advantage, silent mutations make it possible to estimate an unbiased mutation frequency. Since this frequency is at least 100 times higher than would be expected for normal tissue, tumors must be hypermutable. In addition, a class of tumors may be supermutable with a mutation frequency comparable to that observed in the generation of immune diversity.