Table 1.

Genomic Instability in Colorectal Cancer.

Type of Genes	Type of Instability	Genes Involved	Frequency (%)	Comments
Tumour suppressor genes	Chromosomal instability	APC	85	Somatic mutations inactivating both copies of APC are present in most sporadic colorectal cancers; A germ-line mutation in familial adenomatous polyposis with an 80% to 100% lifetime risk of colorectal cancer. Activation of Wnt signaling due to inability to degrade the β-catenin oncoprotein [27,28,29,30,31].
		PTEN	10–15	Germ-line mutations that promote activation of PI3K pathway signaling through loss of function [32,33,34].
		TP53	35–55	Germ-line mutation in Li-Fraumeni syndrome; inactivates missense mutations pairs with loss of heterozygosity at 17p [35,36,37].
		SMAD4	10–35	Germ-line mutation in approximately 40% of juvenile polyposis; a critical component of transforming growth factor β signaling pathway; inactivated by homozygous or mutation with loss of heterozygosity at 18q [38,39,40,41].
	DNA mismatch-repair defects	MLH1, MSH2, MSH6 MYH	15–25	Germ-line mutation permitting the accumulation of oncogenic mutations and tumour suppressor loss [42,43,44].
	Aberrant DNA methylation	MLH1	15	Silencing of the promoter region of the genes in mismatch-repair system by hyper-methylation of CpG islands [45,46].
Oncogenes	DNA mismatch-repair defects	RAS, BRAF	13–37	Activates the mitogen-activated protein kinase signaling pathway [47,48,49].