Table 1.

Patterns of Genomic Instability in Colorectal Cancer.^*

Type of Instability and Syndrome	Type of Defect	Genes Involved	Phenotype
Chromosomal instability – loss of heterozygosity at multiple loci	Somatic	Loss of heterozygosity at APC, TP53, SMAD47,8	Characteristic of 80 to 85% of sporadic colorectal cancers, depending on stage
DNA mismatch-repair defects
Hereditary nonpolyposis colon cancer	Germ-line	MLH1, MSH2, MSH6 germ-line gene mutations9-14	Multiple primary colorectal cancers, accelerated tumor progression, and increased risk of endometrial, gastric, and urothelial tumors
Sporadic colorectal cancer with mismatch-repair deficiency	Somatic	MLH1 somatic methylation15-17	Colorectal cancer with increased risk of poor differentiation, more commonly located in right colon, less aggressive clinical behavior than tumors without mismatch-repair deficiency
CpG island methylator phenotype – methylation target loci	Somatic	Target loci MLH1, MINT1, MINT2, MINT318-23	Characteristic of 15% of colorectal cancers, with most showing mismatch-repair deficiency from loss of tumor MLH1 expression
Base excision repair defect – MYH-associated polyposis	Germ-line	MYH24-26	Development of 15 or more colorectal adenomas with increased risk of colorectal cancer

^*MYH denotes mutY homologue.