Gut Liver.  2016 Sep;10(5):773-780. 10.5009/gnl15334.

Field Cancerization in Sporadic Colon Cancer

• Park SK
• Song CS
• Yang HJ
• Jung YS
• Choi KY
• Koo DH
• Kim KE
• Jeong KU
• Kim HO
• Kim H
• Chun HK
• Park DI

• KMID: 2412075
• DOI: http://doi.org/10.5009/gnl15334

Abstract

BACKGROUND/AIMS
Aberrant DNA methylation has a specific role in field cancerization. Certain molecular markers, including secreted frizzled-related protein 2 (SFRP2), tissue factor pathway inhibitor 2 (TFPI2), N-Myc downstream-regulated gene 4 (NDRG4) and bone morphogenic protein 3 (BMP3), have previously been shown to be hypermethylated in colorectal cancer (CRC). We aim to examine field cancerization in CRC based on the presence of aberrant DNA methylation in normal-appearing tissue from CRC patients.
METHODS
We investigated promoter methylation in 34 CRC patients and five individuals with normal colonoscopy results. CRC patients were divided into three tissue groups: tumor tissue, adjacent and nonadjacent normal-appearing tissue. The methylation status (positive: methylation level >20%) of SFRP2, TFPI2, NDRG4, and BMP3 promoters was investigated using methylation-specific PCR.
RESULTS
The methylation frequencies of the SFRP2, TFPI2, NDRG4 and BMP3 promoters in tumor/adjacent/nonadjacent normal-appearing tissue were 79.4%/63.0%/70.4%, 82.4%/53.6%/60.7%, 76.5%/61.5%/69.2%, 41.2%/35.7%/50.0%, respectively. The methylation levels of the SFRP,TFPI2, NDRG4 and BMP3 promoters in tumor tissues were significantly higher than those in normal-appearing tissue (SFRP2, p=0.013; TFPI2, p<0.001; NDRG4, p=0.003; BMP3, p=0.001). No significant correlation was observed between the methylation levels of the promoters and the clinicopathological variables.
CONCLUSIONS
The field effect is present in CRC and affects both the adjacent and nonadjacent normal-appearing mucosa.

Keyword

Colorectal neoplasms; DNA methylation; Field effect; Epigenomics

MeSH Terms

Biomarkers, Tumor/*genetics
Bone Morphogenetic Protein 3/genetics
Bone Morphogenetic Protein Receptors, Type II/genetics
Case-Control Studies
Colon/pathology
Colonic Neoplasms/*genetics/pathology
Colonoscopy
DNA Methylation/*genetics
Female
Glycoproteins/genetics
Humans
Intestinal Mucosa/pathology
Male
Membrane Proteins/genetics
Middle Aged
Muscle Proteins/genetics
Nerve Tissue Proteins/genetics
Polymerase Chain Reaction
Promoter Regions, Genetic/*genetics
Biomarkers, Tumor
Bone Morphogenetic Protein 3
Glycoproteins
Membrane Proteins
Muscle Proteins
Nerve Tissue Proteins
Bone Morphogenetic Protein Receptors, Type II