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Paper Details


Rabia Farooq, Shajrul Amin, Haamid Bashir, Bashir Ahmad Ganaie, Sabhiya Majid*

Journal Title:World Journal of Pharmaceutical Research

Introduction: Colorectal cancer (CRC) is one of the leading malignancies as being the third most cause of cancer causing death in the world. Carcinogenesis is a complex process caused by various genetic and epigenetic changes in various genes like tumor suppressor genes, DNA repair genes, translation regulatory genes and others. The Wnt/?-catenin pathway plays multiple and diverse roles in development by regulating gene expression via T-cell factor/Lymphoid enhancer-binding factor (Tcf/Lef) DNA binding factors. Misregulation of this pathway is thought to initiate colon adenoma formation. The Wnt pathways with its molecular gladiator Tcf4 plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in Tcf4 gene in the pathogenesis of CRC in the Kashmir valley. Materials and Methods: We examined the paired tumor and normal-tissue specimens of 100 CRC patients from Apr 2010- June 2013, from Department of Surgery, Government Medical College, Srinagar and its associated hospital Shri Maharaja Hari Singh Hospital (SMHS) and analysis of promoter hypermethylation for exon 1 and intron 8 of T cf4 gene was also carried out using Methylation-specific PCR (MS-PCR). Results and Conclusion: Promoter hypermethylation of Tcf4 of the exon 1 of Tcf4 gene among 100 CRC cases was found to be 66 per cent (66 of 100) and for intron 8, it was 70%. Besides in both cases of males and females, the hypermethylation status of intron 8 is more than exon 1 of Tcf4, the study confirms the role of epigenetic gene silencing of th e pivotal molecular gladiator, Tcf4, of the Wnt pathway in the development of CRC in the Kashmiri population. So, it was concluded that Tcf4 promoter may be used as a diagnostic tool for colorectal carcinogenesis and therefore can be used a marker for its diagnosis.