Accumulation of aberrant DNA methylation during colorectal cancer development

Table 1 Colorectal carcinogenic pathways and genetic alterations

	MSI	Methylation	KRAS	BRAF	TP53	Reports
Adenoma-carcinoma sequence	-	+/-	++	-	+	Grady et al[1]
						Vogelstein et al[3]
Serrated pathway	+	++	+	++	+/-	Howkins et al[32]
						Weisenberger et al[35]
De novo pathway	-	-	+	-	-	Yashiro et al[58]
						Kinney et al[59]

MSI: Microsatellite instability.

Table 2 Reports on colorectal cancer classification by methylation information

Ref.	Marker selection	Methylation analysis methods	Classification method	Methylation phenotypes
Toyota et al[20]	Genome-wide (MCA-RDA)	COBRA	Methlation frequency	CIMP+
				CIMP-
Weisenberger et al[35]	MethyLight markers	MethyLight	Hierarchical clustering	CIMP+
				CIMP-
Ogino et al[39]	Reported markers	MethyLight	Methylation frequency	CIMP-high
				CIMP-low
				CIMP-0
Shen et al[13]	Reported markers	Pyrosequence	Hierarchical clustering	CIMP1
		COBRA		CIMP2
		MCA		CIMP-negative
		MSP
Yagi et al[14]	Genome-wide (MeDIP-chip)	MassARRAY	Hierarchical clustering	HME
				IME
				LME
Hinoue et al[12]	Genome-wide (Infinium 27k)	MethyLight	Hierarchical clustering	CIMP-H
				CIMP-L
				Non-CIMP

CIMP: CpG island methylator phenotype; MCA: Methylated CpG island amplication; RDA: Representation difference analysis; COBRA: Combined bisulfite restriction analysis; MSP: Methylation-specific PCR; MeDIP: Methylated DNA immunoprecipitation; LME: Low-methylation epigenotype; IME: Intermediate-epigenotype; HME: High-methylation epigenotype.