Genomic Instability and Colorectal Cancer

Colorectal cancer results from the accumulation of genetic and epigenetic alterations that transform colonic epithelial cells into colon adenocarcinoma cells. The loss of genomic stability appears to be a key molecular and pathogenetic step that occurs early in the tumorigenesis process and permits the acquisition of sufficient alterations in tumor suppressor genes and oncogenes in a clone of cells to result in cancer. Three predominant forms of genomic instability have been identified in colon cancer: 1) microsatellite instability (MSI), 2) chromosome instability (CIN), and 3) chromosomal translocations. Substantial progress has been made recently regarding potential causes of MSI and CIN in colorectal cancer. Furthermore, in addition to genomic instability, a form of epigenomic instability has been recently identified that results in the aberrant methylation of tumor suppressor genes. The discovery of the cause and role of genomic and epigenomic instability in colon cancer formation has the potential to yield more effective chemotherapy strategies for colon cancer.