Table 1.

Genotype-phenotype correlations in colorectal neoplasia

Pathological Lesion	Genetic alteration characteristically present
Adenomatous polyps	Biallelic inactivation of APC (or other mechanism that disrupts control of WNT signaling)
Flat adenoma	APC inactivation
Pedunculated adenoma	APC inactivation plus K-RAS mutation
Villoglandular adenoma	APC inactivation plus K-RAS mutation
Serrated polyps
Hyperplastic polyp	K-RAS mutation (but no APC lesions)
Serrated adenoma	CIMP and BRAF mutations
Colorectal Cancer	Chromosomal instability (CIN), with mutations in APC, K-RAS, and p53 Microsatellite instability (MSI) with insertion- deletion mutations in repetitive DNA sequence (i.e., microsatellites); requires inactivation of the DNA mismatch repair system. Target gene mutations in TGFβ1RII, BAX, etc. CpG island methylator phenotype (CIMP) with epigenetic silencing of multiple genes (including p16, MGMT, MLH1, BRCA1, E-cadherin, APC, PTEN, etc.
Flat Colorectal Cancers	APC and p53 alterations, without K-RAS mutations
Aberrant Crypt Foci	K-RAS mutations, without APC alterations