{"entity":{"id":"cimp","kind":"term","name":"CpG island methylator phenotype (CIMP)","aka":["CIMP","CpG island methylator phenotype","CIMP-high","CIMP-low","hypermethylated colorectal cancer"],"tldr":"Some bowel cancers switch off large numbers of genes at once by chemically tagging their control regions rather than by mutating them. That state travels with BRAF mutation, with the serrated route to cancer and with the accidental loss of DNA proofreading, and it is how most bowel cancers with unstable microsatellites arise without an inherited fault.","summary":"What it is. Methylation of cytosines in the CpG-rich control regions of genes silences them. A subset of colorectal tumours methylates an exceptionally high number of such islands, a state named the CpG island methylator phenotype. The original description separated islands methylated with age in normal colon from those methylated only in cancer, and showed that the cancer-specific ones clustered in a subset of tumours that also methylated p16 and THBS1 and included most sporadic microsatellite-unstable cancers, through methylation of MLH1 (Toyota 1999).\n\nThe evidence that settled the argument. The existence of CIMP as a distinct group was disputed until a systematic screen of 195 methylation markers across 295 tumours, with 16,785 quantitative analyses, showed that positive tumours form a distinct subset that encompasses almost every BRAF-mutant colorectal cancer (odds ratio 203), and that sporadic mismatch repair deficiency occurs almost exclusively through CIMP-associated methylation of MLH1. That study proposed the marker panel now used to classify it (Weisenberger 2006).\n\nWhere it sits. CIMP is the molecular fingerprint of the serrated pathway, which accounts for about 30 percent of colorectal carcinomas and runs through sessile serrated lesions with BRAF mutation. It is the reason an older person with a right-sided, mismatch repair-deficient tumour usually does not have Lynch syndrome: testing for MLH1 promoter methylation and BRAF V600E separates the sporadic from the inherited before germline testing is considered. It is not a test the health service reports for its own sake; it explains the tests that are reported.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/CpG_site","links":[{"label":"Toyota, PNAS 1999: CpG island methylator phenotype in colorectal cancer","url":"https://doi.org/10.1073/pnas.96.15.8681"},{"label":"Weisenberger, Nat Genet 2006: the CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation (295 tumours)","url":"https://doi.org/10.1038/ng1834"},{"label":"Bettington, Histopathology 2013: the serrated pathway to colorectal carcinoma, current concepts and challenges","url":"https://doi.org/10.1111/his.12055"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","msi-high-colorectal","braf-v600e-colorectal","colorectal-serrated-adenocarcinoma","colon-cancer"],"sections":[],"technologies":["msi-mmr-testing","histopathology-ihc"],"targets":["braf"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["serrated-pathway","mlh1-promoter-methylation","msi","lynch-syndrome","cms-subtypes","sidedness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},"route":"/terms/cimp/","neighbours":{"cancer":[{"id":"braf-v600e-colorectal","kind":"cancer","name":"BRAF V600E-mutant colorectal cancer","route":"/cancers/braf-v600e-colorectal/"},{"id":"colon-cancer","kind":"cancer","name":"Colon cancer (adenocarcinoma of the colon)","route":"/cancers/colon-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"msi-high-colorectal","kind":"cancer","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","route":"/cancers/msi-high-colorectal/"},{"id":"colorectal-serrated-adenocarcinoma","kind":"cancer","name":"Serrated adenocarcinoma of the colon and rectum","route":"/cancers/colorectal-serrated-adenocarcinoma/"}],"technology":[{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"msi-mmr-testing","kind":"technology","name":"MSI and mismatch-repair testing","route":"/technologies/msi-mmr-testing/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"}],"term":[{"id":"cms-subtypes","kind":"term","name":"Consensus molecular subtypes (CMS1-4)","route":"/terms/cms-subtypes/"},{"id":"lynch-syndrome","kind":"term","name":"Lynch syndrome","route":"/terms/lynch-syndrome/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"mlh1-promoter-methylation","kind":"term","name":"MLH1 promoter methylation (sporadic versus Lynch mismatch repair loss)","route":"/terms/mlh1-promoter-methylation/"},{"id":"serrated-pathway","kind":"term","name":"Serrated pathway","route":"/terms/serrated-pathway/"},{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"}]}}