CIMP

CpG island methylator phenotype, abbreviated as CIMP, refers to a molecular cancer subtype characterized by widespread hypermethylation of promoter CpG islands across a set of genes, leading to transcriptional silencing. The phenotype is described in terms of CIMP-high, CIMP-low, and CIMP-negative categories in some tumor types, and it is identified through genome-wide or targeted DNA methylation profiling. CIMP represents a distinct epigenetic pattern rather than random focal methylation or global hypomethylation observed in many cancers.

In colorectal cancer, CIMP was among the first cancer contexts where this pattern was defined. CIMP-high tumors frequently display promoter methylation of multiple genes such as MLH1, which can drive microsatellite instability, and are often associated with BRAF V600E mutations. However, definitions and panels used to classify CIMP vary by study, complicating cross-study comparisons. Detection methods include methylation-specific PCR, bisulfite sequencing, and array- or sequencing-based methylation profiling.

In gliomas, a related methylator phenotype is referred to as G-CIMP (glioma-CpG island methylator phenotype). G-CIMP is strongly associated with IDH1 or IDH2 mutations and MGMT promoter methylation, and it has been linked to younger patient age and, in some cohorts, improved prognosis. G-CIMP has become part of the molecular framework for glioma classification.

CIMP-like patterns have also been reported in other cancers such as gastric cancer and hepatocellular carcinoma, but the definition and clinical significance are more variable across tumor types. Overall, CIMP is used to categorize tumors with concerted promoter hypermethylation and contributes to insights into tumor biology, classification, and potential prognostic or therapeutic implications.