Table 2.

Comparison of type of mismatch repair gene mutations between sporadic hypermethylated MLH1 colorectal cancers and POLE mutation colorectal cancers from TCGA

MLH1 promoter hypermethylation	22/35 (63%) of hypermutated CRCs	8/22 (36%) with MSH3 frameshift mutation
		1/22 (4.5%) with MSH3 missense/nonsense mutation
		0/22 (0%) with MSH2 mutation
		5/22 (23%) with MSH6 frameshift mutation
		4/22 (18%) with MSH6 missense/nonsense mutation
POLE mutation	13/35 (37%) of hypermutated CRCs	3/13 (23%) with MSH3 frameshift mutation
		2/13 (15%) with MSH3 missense/nonsense mutation
		5/13 (38%) with MSH2 missense/nonsense mutation
		0/13 (0%) with MSH6 frameshift mutation
		7/13 (54%) with MSH6 missense/nonsense mutation

Both types of CRCs are hypermutated, containing hundreds of somatic mutations in genomic DNA. Note that the MLH1 hypermethylated CRCs demonstrate higher frequency and consistent frameshift mutations in MSH3 and MSH6 as compared to POLE mutated CRCs, which contain some frameshifts but higher frequency of missense/nonsense mutations in MSH3, MSH2 and MSH6. Extracted from: Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012; 487: 333-337. CRCs: Colorectal cancers.