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  • Title: Urothelial carcinomas arising in arsenic-contaminated areas are associated with hypermethylation of the gene promoter of the death-associated protein kinase.
    Author: Chen WT, Hung WC, Kang WY, Huang YC, Chai CY.
    Journal: Histopathology; 2007 Dec; 51(6):785-92. PubMed ID: 17953697.
    Abstract:
    AIMS: The mechanisms of urothelial carcinogenesis in areas highly contaminated with arsenic remain unclear. The aim was to determine whether hypermethylation of death-associated protein kinase (DAPK) gene is associated with chronic arsenic exposure. METHODS AND RESULTS: The frequency of aberrant promoter methylation of DAPK in 17 urothelial carcinomas from an arsenic-contaminated area and 21 urothelial carcinomas from a non-arsenic-contaminated area was determined by methylation-specific polymerase chain reaction. DAPK hypermethylation status was significantly higher in urothelial cancers arising in arsenic-contaminated areas when compared with tumours from patients from non-contaminated areas (P = 0.018). In the subset of patients from living environments which were contaminated with arsenic, there was a statistically significant association between DAPK hypermethylation and patient's age, tumour invasiveness, histological grade and recurrence. This was not seen for urothelial carcinoma from patients from non-contaminated areas. A close correlation was also found between DAPK promoter methylation and low-intensity DAPK expression, as detected by immunohistochemistry (P = 0.037). CONCLUSION: Exposure to arsenic may induce DAPK promoter hypermethylation and inactivate the function of DAPK in urothelial carcinoma. This could prove to be a key molecular event contributing to the malignant phenotype of tumour arising in patients from arsenic-contaminated environments.
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