Field Cancerization in Sporadic Colon Cancer.
- Author:
Soo Kyung PARK
1
;
Chang Seok SONG
;
Hyo Joon YANG
;
Yoon Suk JUNG
;
Kyu Yong CHOI
;
Dong Hoe KOO
;
Kyung Eun KIM
;
Kyung Uk JEONG
;
Hyung Ook KIM
;
Hungdai KIM
;
Ho Kyung CHUN
;
Dong Il PARK
Author Information
- Publication Type:Original Article
- Keywords: Colorectal neoplasms; DNA methylation; Field effect; Epigenomics
- MeSH: Colon*; Colonic Neoplasms*; Colonoscopy; Colorectal Neoplasms; DNA Methylation; Epigenomics; Humans; Methylation; Mucous Membrane; Polymerase Chain Reaction; Thromboplastin
- From:Gut and Liver 2016;10(5):773-780
- CountryRepublic of Korea
- Language:English
- 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.
