What is a Methylator phenotype?
CpG island methylator phenotype (CIMP) is a subset of colorectal cancers that happen through an epigenetic instability pathway and that are characterized by vast hypermethylation of promoter CpG island sites, resulting in the inactivation of several tumor suppressor genes or other tumor-related genes (17).
Why are CpG islands important for epigenetic memory?
CpG islands, for example, keep their overall unmethylated state (or methylated state) extremely stably through multiple cell generations. DNMT1 is partly responsible for this stability, but there is likely to be another as yet unknown component to the maintenance process.
What does CpG island stand for?
CpG islands (or CG islands) are regions with a high frequency of CpG sites. Though objective definitions for CpG islands are limited, the usual formal definition is a region with at least 200 bp, a GC percentage greater than 50%, and an observed-to-expected CpG ratio greater than 60%.
What causes CIMP?
Occurrence of CIMP is associated with a range of genetic and environmental factors, although the molecular causes are not well-understood. Both increased expression and aberrant targeting of DNA methyltransferases (DNMTs) could contribute to the occurrence of CIMP.
What is MSI and MMR?
Background: Micro-Satellite Instability (MSI) or DNA Mismatch Repair (MMR) is an established prognostic test associated with response to chemotherapies in Lynch Syndrome, colorectal cancer and other indications. Recently, MSI/MMR status has been shown to predict response to immune checkpoint inhibitors (CPI).
When are CpG island methylated?
The presence of multiple methylated CpG sites in CpG islands of promoters causes stable silencing of genes. Silencing of a gene may be initiated by other mechanisms, but this is often followed by methylation of CpG sites in the promoter CpG island to cause the stable silencing of the gene.
How does methylation of CpG islands affect gene expression?
The role of CpG islands in regulating gene expression is still being uncovered. Methylation of CpG islands can impair transcription factor binding, recruit repressive methyl-binding proteins, and stably silence gene expression.
What is DNA methylation CpG islands?
DNA methylation is an epigenetic mark that plays an essential role in regulating gene expression. CpG islands are DNA methylations regions in promoters known to regulate gene expression through transcriptional silencing of the corresponding gene.