The CpG island methylator phenotype is concordant between primary colorectal carcinoma and matched distant metastases

Clin Epigenetics. 2017 May 2:9:46. doi: 10.1186/s13148-017-0347-1. eCollection 2017.


Background: The CpG island methylator phenotype (CIMP) in stage III colon cancer (CRC) has been associated with improved survival after treatment with adjuvant irinotecan-based chemotherapy. In this analysis, we determine whether CIMP status in the primary CRC is concordant with the CIMP status of matched metastases in order to determine if assessment of CIMP status in the primary tumor can be used to predict CIMP status of metastatic disease, which is relevant for patient management as well as for understanding the biology of CIMP CRCs.

Methods: We assessed the CIMP status of 70 pairs of primary CRC and matched metastases using a CRC-specific panel of five markers (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1) where CIMP positive was defined as 3/5 positive markers at a percent methylated reference threshold of ≥10%. Concordance was compared using the Fisher's exact test and P < 0.05 was considered significant.

Results: Sixty-nine of the pairs (98.6%) showed concordant CIMP status in the primary tumor and matched metastasis; five (7.0%) of the pairs were concordantly CIMP positive. Only one pair (1.4%) had divergent CIMP status, demonstrating CIMP positivity (4/5 markers positive) in the primary tumor, while the matched metastasis was CIMP negative (0 markers positive).

Conclusions: CIMP status is generally concordant between primary CRCs and matched metastases. Thus, CIMP status in the primary tumor is maintained in matched metastases and can be used to inform CIMP-based therapy options for the metastases.

Keywords: Biomarker; CIMP; Colorectal cancer; DNA methylation; Metastatic.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Biomarkers, Tumor / genetics*
  • Calcium Channels, T-Type / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Core Binding Factor Alpha 3 Subunit / genetics
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Nerve Tissue Proteins / genetics
  • Phenotype
  • Suppressor of Cytokine Signaling 1 Protein / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • CACNA1G protein, human
  • Calcium Channels, T-Type
  • Core Binding Factor Alpha 3 Subunit
  • IGF2 protein, human
  • NEUROG1 protein, human
  • Nerve Tissue Proteins
  • Runx3 protein, human
  • SOCS1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Insulin-Like Growth Factor II