Fig. 5
From: A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer
Our model of colorectal cancer evolution. During early tumorigenesis, multiple subclones harboring heterogeneous mutations on different driver genes appear and constitute ITH by Darwinian evolution. The tumor is then confronted with growth limitation before progressing to the late phase of tumorigenesis. Out of the multiple subclones generated by Darwinian evolution, the parental clone that can conquer the growth limitation emerges. In addition to a sufficient set of driver single-nucleotide mutations, such a clone possibly acquires driver CNAs. The parental clone is selected to progress locally advanced cancer or metastatic cancer. During the late phase, extensive ITH is generated by neutral evolution
