Implication of alterations in Parkin gene among North Indian patients with colorectal cancer

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Background/Aims: Alterations in Parkin (PRKN) have been described in many cancers; however, the molecular mechanism that contributes to loss of Parkin expression in colorectal cancer (CRC) remains unclear. The aim of this study was to investigate the involvement ofPRKN mutation and loss of heterozygosity (LOH) in loss of Parkin expression. To understand the role of PRKN in cancer progression, wealso evaluated the association of Parkin expression with clinicopathological parameters in North Indian population.Materials and Methods: We studied 219 CRC samples and their adjacent normal tissues (control) obtained from North Indian patientswith CRC. The expression of Parkin was analyzed by immunohistochemistry (IHC). PRKN mutations were analyzed by single-stranded conformational polymorphism (SSCP) and sequencing. For loss of heterozygosity (LOH), we employed two intragenic, D6S305 andD6S1599, and one telomeric marker, D6S1008.Results: In our study, we found four novel somatic mutations, namely, C166G, K413N, R420P (exon 4), and V425E (exon 11). Bothmutation in Parkin (p = 0.0014) and LOH (p = 0.0140) were significantly associated with loss of Parkin expression. Additionally, Parkinmutations were not associated with the clinicopathological parameters of the patients. Furthermore, both, LOH in Parkin and Parkinexpression were significantly correlated with different clinicopathological variables (p<0.05).Conclusion: Our results indicate that Parkin expression is not regulated by a single mechanism, but both mutation and LOH contributeto loss of Parkin expression. We also provide evidence of involvement of Parkin in metastasis and cancer progression. We, therefore,suggest Parkin as a potential prognostic marker and warrant further analysis in this direction