The methylator phenotype in microsatellite stable colorectal cancers is characterized by a distinct gene expression profile

J Pathol. 2008 Apr;214(5):594-602. doi: 10.1002/path.2318.


The CpG island methylator phenotype (CIMP) in colorectal tumours can be recognized by an increased frequency of aberrant methylation in a specific set of genomic loci. Because of the strong association of CIMP with high microsatellite instability (MSI-H), the identification of CIMP+ tumours within microsatellite stable (MSS) colorectal cancers may not be straightforward. To overcome this potential limitation, we have built an improved seven-locus set of methylation markers that includes CACNA1G, IGF2, RUNX3, HTR6, RIZ1, MINT31, and MAP1B. This new set of CIMP markers revealed a bimodal distribution of methylation frequencies in a group of 95 MSS colorectal cancers, which allowed a clearer separation between CIMP classes. Correlation of MSS CIMP+ tumours with bio-pathological traits revealed significant associations with location to the proximal colon, mucinous histology, BRAF mutation, and chromosomal stability. A potential trend towards an adverse prognosis of CIMP+ cases was associated with the high frequency of BRAF mutations present within this cohort of tumours. Microarray analysis revealed that CIMP+ tumours are characterized by a unique expression profile, a result that confirms that CIMP+ tumours represent a truly distinct molecular class within MSS colorectal cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cluster Analysis
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • CpG Islands / genetics
  • DNA Methylation*
  • DNA, Neoplasm / genetics*
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling
  • Genetic Markers
  • Humans
  • Male
  • Microsatellite Instability
  • Microsatellite Repeats / genetics*
  • Mutation
  • Oligonucleotide Array Sequence Analysis / methods
  • Phenotype
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics


  • DNA, Neoplasm
  • Genetic Markers
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf