MUC2: the Major Target Gene for the MSI in Colorectal Carcinoma

Arfaoui A, Trabelsi M, Aloui R, Blel A, Farah F, Rammeh S, Zidi Y, Zneidi N, Zarmeni R, Kourda N

Abstract


The recent discovery of hypermethylation of the promoter of genes is a powerful epigenetic mechanism for the inactivation of some genes in colorectal and other cancers. Approximately, 95% of hereditary non-polyposis colorectal cancers (HNPCCs) and 15% of sporadic colorectal cancers (CRCs) are instable in their Mismatch repair system (MMR).
we analyzed by immunohistochemistry the immunostaining of MUC2 and MMR genes.
Herein, we have shown that the MSI phenotype, resulting in the deficiency of a capital genes of MMR system such as MLH1, MSH2, MSH6 and PMS2. Moreover, all CRCs were found to be hypermethylated in the MUC2 promoter and this correlated with negative E-cadherin expression and especially microsatellite instability.
MSS cancers tend to be diploid or near diploid karyotype with similar mutations in the APC and K-Ras genes but reduced mutations in p53. Mutations found in MSI cancers but not MSS cancers include the TGF-β, IGFII, BAX and E2F4 genes and now MUC2. MUC2 appears to be a typical target gene of MSI phenotype in Tunisian patients with CRCs.
Knowing that the Hypermethylation of the promoter may be reversed and gene function restored to a cell, identification of epigenetic alterations can be a powerful therapeutic approach throughout the inhibition of DNA-methylase enzyme.

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