CpG Island Methylator Phenotype-A Hope for the Future or a Road to Nowhere?

Int J Mol Sci. 2022 Jan 13;23(2):830. doi: 10.3390/ijms23020830.

Abstract

The CpG island methylator phenotype (CIMP) can be regarded as the most notable emanation of epigenetic instability in cancer. Since its discovery in the late 1990s, CIMP has been extensively studied, mainly in colorectal cancers (CRC) and gliomas. Consequently, knowledge on molecular and pathological characteristics of CIMP in CRC and other tumour types has rapidly expanded. Concordant and widespread hypermethylation of multiple CpG islands observed in CIMP in multiple cancers raised hopes for future epigenetically based diagnostics and treatments of solid tumours. However, studies on CIMP in solid tumours were hampered by a lack of generalisability and reproducibility of epigenetic markers. Moreover, CIMP was not a satisfactory marker in predicting clinical outcomes. The idea of targeting epigenetic abnormalities such as CIMP for cancer therapy has not been implemented for solid tumours, either. Twenty-one years after its discovery, we aim to cover both the fundamental and new aspects of CIMP and its future application as a diagnostic marker and target in anticancer therapies.

Keywords: CIMP; DNA methylation; epigenetics; methylator phenotype.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Biomarkers, Tumor
  • Computational Biology / methods
  • CpG Islands*
  • DNA Methylation*
  • Drug Development
  • Epigenesis, Genetic*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Humans
  • Molecular Targeted Therapy
  • Oligonucleotide Array Sequence Analysis
  • Phenotype

Substances

  • Biomarkers
  • Biomarkers, Tumor