CpG Island Methylator Phenotype in Cancer

Abstract

Aberrant deoxyribonucleic acid (DNA) methylation is an important epigenetic change in various cancers. During carcinogenesis, DNA methylation preferentially occurs in promoter CpG islands, which do not usually undergo DNA methylation in normal cells. Promoter CpG island methylation causes transcriptional silencing of the corresponding gene and is thus regarded as one of the mechanisms of tumour suppressor gene inactivation. In human cancers, the unique molecular phenotype characterised by extensive promoter CpG islands hypermethylation has been referred to as the CpG island methylator phenotype (CIMP). Although characteristic clinicopathological and molecular associations of CIMP have been identified in some types of malignancies, there has been a lack of consensus regarding the diagnostic criteria for CIMP, and prognostic/predictive values of CIMP in cancers have been controversial.

Key Concepts

  • Aberrant DNA methylation is one of the molecular hallmarks of cancers.
  • The CpG island methylator phenotype (CIMP) indicates a subtype of cancer characterised by widespread promoter CpG islands methylation.
  • CIMP has been identified representatively in colorectal cancers, gastric cancers and brain gliomas.
  • CIMP+ colorectal cancers are associated with the serrated neoplasia pathway and poor prognosis, but the predictive value of CIMP remains controversial.
  • CIMP+ gastric cancers are associated with Epstein–Barr virus (EBV) positivity and/or microsatellite instability‐high (MSI‐H) status.
  • CIMP+ gliomas are associated with isocitrate dehydrogenase (IDH) mutations.

Keywords: epigenetics; DNA methylation; CpG island methylator phenotype; colorectal cancer; gastric cancer; glioma

Figure 1. A model of clinicopathological and molecular features of the developmental sequence of CpG island methylator phenotype (CIMP)‐high colorectal carcinoma. CIMP‐high colorectal carcinoma is closely associated with the serrated neoplasia pathway, which is characterised by unique precursor lesions (sessile serrated adenomas) and molecular factors (BRAF mutations and MSI‐high).
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Kim, Jung H, Bae, Jeong M, and Kang, Gyeong H(Jan 2017) CpG Island Methylator Phenotype in Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026338]