Genomic-Destabilization-Associated Mutagenesis and Clonal Evolution of Cells with Mutations in Tumor-Suppressor Genes

The development of cancer is driven by genomic instability and mutations. In general, cancer develops via multiple steps. Each step involves the clonal evolution of cells with abrogated defense systems, such as cells with mutations in cancer-suppressor genes. However, it remains unclear how cellular defense systems are abrogated and the associated clonal evolution is triggered and propagated. In this manuscript, we review current knowledge regarding mutagenesis associated with genomic destabilization and its relationship with the clonal evolution of cells over the course of cancer development, focusing especially on mechanistic aspects.