Significant Pattern of Promoter Hypermethylation of UNC5C Gene in Colorectal Cancer and Its Implication in Late Stage Disease

Background:The development of Colorectal Cancer (CRC) is a complex multistep process involving an accumulation of multiple genetic and epigenetic alterations. Epigenetic modifications, particularly DNA methylation in selected gene are recognized as common molecular alterations in human tumors. Netrin-1 receptors are aberrantly methylated in primary colorectal cancer. Epigenetic alterations in the netrin-1 receptors have been found to be related with the malignant potential of CRC. Purpose: In the present study, we evaluated the role of promoter hypermethylation of UNC5C gene (one of the netrin-1 receptors) in colorectal cancer patients of Kashmiri population (North India). Hypermethylation in tumour tissue was detected by Methylation- Specific Polymerase Chain Reaction (MS-PCR). Results: UNC5C promoter hypermethylation was significantly found to be associated with colorectal cancer cases where frequency was 62% (31 of 50) and 38% (19 of 50) patients were unmethylated (p<0.0001).UNC5C methylation was significantly higher in CRCs with a frequency of 62% than 10% in corresponding normal mucosa of (p<0.0001). Further, UNC5C hypermethylation was found to be significantly associated with stage-III/IV as compared to stage I/II with a frequency of 75.8% and 42.8% respectively(p>0.05). Conclusion: We conclude that UNC5C hypermethylation is implicated in CRC which plays a role in its tumorigenesis and may predict the late stage disease.