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Updated: Aug 7, 2026

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF
Daniel J Weisenberger1, Kimberly D Siegmund, Mihaela Campan
1Department of Surgery, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90089-9176, USA.
Abstract:
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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