S-Space College of Medicine/School of Medicine (의과대학/대학원) Pathology (병리학전공) Journal Papers (저널논문_병리학전공)
CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer
- Issue Date
- Nature Publishing Group
- Nat. Genet. 38(7), 787-793 (2006).
- Colorectal Neoplasms/*genetics ; DNA Repair/genetics ; DNA, Neoplasm/chemistry/genetics ; Epigenesis, Genetic ; Gene Silencing ; Genomic Instability ; Humans ; Microsatellite Repeats ; Models, Genetic ; Phenotype ; Promoter Regions, Genetic ; Proto-Oncogene Proteins B-raf/*genetics ; CpG Islands ; DNA Methylation ; Mutation
- Aberrant DNA methylation of CpG islands has been widely observed in human colorectal tumors and is associated with gene silencing when it occurs in promoter areas. A subset of colorectal tumors has an exceptionally high frequency of methylation of some CpG islands, leading to the suggestion of a distinct trait referred to as 'CpG island methylator phenotype', or 'CIMP'. However, the existence of CIMP has been challenged. To resolve this continuing controversy, we conducted a systematic, stepwise screen of 195 CpG island methylation markers using MethyLight technology, involving 295 primary human colorectal tumors and 16,785 separate quantitative analyses. We found that CIMP-positive (CIMP+) tumors convincingly represent a distinct subset, encompassing almost all cases of tumors with BRAF mutation (odds ratio = 203). Sporadic cases of mismatch repair deficiency occur almost exclusively as a consequence of CIMP-associated methylation of MLH1 . We propose a robust new marker panel to classify CIMP+ tumors.
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