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ORIGINAL ARTICLE
Year : 2016  |  Volume : 143  |  Issue : 7  |  Page : 82-90

Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer


1 Centre for Genomics; School of Studies in Zoology, Jiwaji University, Gwalior, Madhya Pradesh, India
2 Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, India
3 Department of Pathology, Cancer Hospital and Research Institute, Gwalior, Madhya Pradesh, India
4 Department of Surgical Oncology, Cancer Hospital and Research Institute; Department of Surgery, Gajra Raja Medical College, Gwalior, Madhya Pradesh, India

Correspondence Address:
Pramod Kumar Tiwari
Centre for Genomics, Molecular and Human Genetics, School of Studies in Zoology, Jiwaji University, Gwalior 474 011, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-5916.191792

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Background & objectives: Loss of function of adenomatous polyposis coli (APC) has been reported in cancer. The two promoters of APC, 1A and 1B also have roles in cancer. But, the epigenetic role of APC promoters is not yet clear in gallbladder cancer (GBC) and gallstone diseases (GSD). We undertook this study to determine the epigenetic role of APC in GBC and GSD. Methods: Methylation-specific (MS)-PCR was used to analyze the methylation of APC gene. The expression of APC gene was studied by semi-quantitative PCR, real-time PCR and immunohistochemistry (IHC) in GBC, GSD and adjacent normal tissues. Results: Of the two promoters, APC 1A promoter was found methylated in 96 per cent GBC ( P=0.0155) and 80 per cent GSD (P=0.015). Exon 1 was downregulated in grade II (P=0.002) and grade III (P=0.0001) of GBC, while exon 2 was normally expressed. Scoring analysis of IHC revealed 0 or negativity in 34.48 per cent (P=0.057) and 1+ in 24.14 per cent (P=0.005) GBC cases suggesting loss of APC expression. Interpretation & conclusions: The present findings indicate epigenetic silencing of APC in advanced GBC. The methylation pattern, followed by expression analysis of APC may be suggested for diagnostic, prognostic and therapeutic purposes in GBC in future.


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