Background: Progression of breast cancer involves both genetic and epigenetic factors. Parkin gene has been\nidentified as a tumor suppressor gene in the pathogenesis of various cancers. Nevertheless, the putative role of\nParkin in breast cancer remains largely unknown. Therefore, we evaluated the regulation of Parkin through both\ngenetic and epigenetic mechanisms in breast carcinoma.\nMethod: A total of 156 breast carcinoma and their normal adjacent tissue samples were included for mutational\nanalysis through SSCP, and sequencing. MS-PCR was employed for methylation study whereas Parkin protein\nexpression was evaluated using immunohistochemistry and western blotting. For the survival analysis, Kaplanâ??Meier\ncurve and Coxâ??s proportional hazard model were used.\nResults: In expression analysis, Parkin protein expression was found to be absent in 68% cases of breast cancer. We\nfound that aberrant promoter methylation of Parkin gene is a frequent incident in breast cancer tumors and cell\nlines. Our MS-PCR result showed that Parkin promoter methylation has a significant role (p = 0.0001) in reducing the\nexpression of Parkin protein. Consistently, expression of Parkin was rectified by treatment with 5-aza-2-\ndeoxycytidine. We also found significant associations of both Parkin negative expression and Parkin promoter\nmethylation with the clinical variables. Furthermore, we found a very low frequency (5.7%) of Parkin mutation with\nno clinical significance. In survival analysis, patients having Parkin methylation and Parkin loss had a worse outcome\ncompared to those harboring none of these events.\nConclusion: Overall, these results suggested that promoter methylation-mediated loss of Parkin expression could\nbe used as a prognostic marker for the survival of breast cancer.
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