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

Document Type: Research Articles

Authors

1 Department of General And Minimal Invasive Surgery, Sher-I-Kashmir Institute of Medical Sciences (SKIMS) Srinagar, Kashmir, India.

2 Department of Immunology and Molecular Medicine, SKIMS, India.

3 Advanced Centre for Human Genetics, SKIMS, India.

Abstract

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.

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