Genomic instability, DNA methylation, and natural selection in colorectal carcinogenesis

Neoplastic transformation is increasingly understood in terms of evolutiona ry mechanisms, and it is now widely accepted that tumor progression involve s natural selection of genetic variants occurring in the somatic environmen t. Here we give a review of data that substantiate this Darwinian view to t umorigenesis, with particular emphasis on recent advances related to colore ctal cancer. We specifically focus on the controversies related to genomic instability and DNA methylation, and present a model, which interrelates th ese phenomena to the basic evolutionary concept of biology.