CpG island methylator phenotype in adenocarcinomas from the digestive tract: Methods, conclusions, and controversies

Table 1 Overview of previous studies of CpG island methylator phenotype in tumors from the gastrointestinal track

Year	Event	Ref.
1999	CIMP is first reported in a set of CRC patients	[5]
2004	Nature Reviews paper discussing CIMP in a variety of tumors besides CRC	[23]
2006	Refined molecular subtyping includes CIMP-low and CIMP-0 categories in CRC, with associations to KRAS mutations	[47]
	New insights are gained about the interplay between BRAF V600E mutations, MSI status, MLH1 promoter methylation and CIMP in CRC	[14]
2006-2012	High throughput DNA methylation arrays become widely available, enabling the use of larger gene panels for CIMP characterization	[45,46]
2014	TCGA marker paper on gastric cancer highlights the biological relevance of CIMP for molecular subtyping, exploring associations with EBV infection	[64]
	A better mechanistic understanding of CIMP in CRC is gained through elucidation of the role of MAFG in the context of MLH1 silencing and BRAF V600E mutations	[76]
2015	Pan-cancer stratification of solid tumors reveals similarities in CIMP across a wide variety of cancer types	[51]

CIMP: CpG island methylator phenotype; CRC: Colorectal cancer; MSI: Microsatellite instability; TCGA: The Cancer Genome Atlas.