 In an average melanoma tissue sample (where melanomas have a higher exome mutation frequency) the total number of DNA sequence mutations is about 80,000.The high frequency of mutations in the total genome within cancers suggests that, often, an early carcinogenic alteration may be a deficiency in DNA repair.Mutation rates substantially increase (sometimes by 100-fold) in cells defective in DNA mismatch repair or in homologous recombinational DNA repair.