DNA hypermethylation of a selective gene panel as a risk marker for colon cancer in patients with ulcerative colitis.

Patients with inflammatory bowel disease (IBD) which includes ulcerative colitis (UC) and Crohn's disease (CD) of the colon are at risk of developing colorectal cancer (CRC). Here, we analyzed the methylation status of selected genes as a risk marker in UC patients. We assessed methylation frequency of 4 genes [secreted frizzled-related protein 1 (SFRP1), transcription elongation regulator 1-like (TCERG1L), fibrillin 2 (FBN2) and tissue factor pathway inhibitor 2 (TFPI2)] in biopsies of 36 UC patients. SFRP1 and TCERG1L genes showed high methylation frequencies but FBN2 and TFPI2 genes showed methylation frequencies of 50% in UC patients which suggests that our sensitive selective markers could detect half of the UC patients. We also confirmed the methylation status in UC tissues by bisulfite sequencing analysis. We compared the levels of methylation in terms of quantification between UC patients and CRC tumors. Importantly, methylation levels of these 4 genes were found to be significantly higher in CRC compared to UC patients, even though we noted a frequent methylation pattern in UC patients. Our data suggest that sensitive DNA methylation markers are able to identify UC patients and this would implicate the risk of CRC. Therefore, assessing the methylation of these 4 genes in UC patients could contribute to prevent the progression of severe disease with regular colonoscopic surveillance.