Estimation of mutation frequencies in normal mammalian cells and the development of cancer

A current controversy in cancer research is whether the rate of accumulation of mutations in normal somatic cells is sufficient to account for the number of mutations in malignant cells. This review will focus on the types of mutations that can occur in mammalian somatic cells and the frequency at which some of these mutations have been shown to occur in vivo. Human and mouse mutation detection systems will be highlighted. The possibility that distinct mutational events can arise from a common precursor will be discussed, as will the possibility that inherited and sporadic cancers can acquire mutator phenotypes at different times in tumor development. Consideration will also be given to a potential relationship between an age-related accumulation of mutations and cancer.