Evolution of cancer genes as a mutation-driven process.

Cancer is primarily a somatic genetic disease resulting from the accumulation of several precancerous mutations in a cell lineage. The evolution of highly oncogenic retroviruses has been used as a model for the evolution of a cancer cell. The properties of intermediates between one set of replication-competent retrovirus and protooncogene progenitors and the homologous highly oncogenic retrovirus were analyzed to differentiate between selection-driven and mutation-driven models of this evolution. In this case and in some other cases where sufficient data are available, it appears that the intermediates in the evolution of highly oncogenic retroviruses are not transforming, indicating that they were not formed in a purely selection-driven process. Furthermore, analysis of retrovirus mutation rates indicates that there is a high rate of mutation in retrovirus replication such that the evolution of highly oncogenic retroviruses could be mutation-driven. Other evidence is mentioned suggesting that oncogenesis in general is at least partially mutation-driven, although mutational mechanisms are involved that are different from those involved in the evolution of highly oncogenic retroviruses.