| Summary: | <p>Abstract</p> <p>The development and progression of colorectal cancer (CRC) is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (<it>APC</it>) and <it>β-catenin </it>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 the <it>APC </it>and <it>β-catenin </it>genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR) of the <it>APC </it>gene and exon 3 of the β-<it>catenin </it>gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the <it>APC </it>gene was also carried out using methylation-specific PCR (MS-PCR). The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86). Promoter hypermethylation of <it>APC </it>was observed in 54.65 per cent (47 of 86) of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the <it>APC </it>gene (<it>p </it>≤ 0.05). Although the number of mutations in the <it>APC </it>and <it>β-catenin </it>genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, <it>APC</it>, of the Wnt pathway in the development of CRC in the Kashmiri population.</p>
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