BACKGROUND: Death-associated protein kinase (DAPK) is a Ca2+/calmodulin-regulated Ser/Thr kinase which is involved in apoptosis. The aberrant methylation of its promoter region CpG islands may be one of the important mechanisms of carcinogenesis. We studied the relationship of methylation status and expression of the DAPK gene with the clinical findings in cholangiocarcinoma.
METHODS: Target DNA was modified by sodium bisulfite, coverting all unmethylated, but not methylated, cytosines to uracil, and subsequently detected by methylation-specific PCR. Moreover, mRNA expression of the DAPK gene was assessed by RT-PCR.
RESULTS: Aberrant methylation of the DAPK gene was detected in 11 (30.6%) of 36 tissue specimens of cholangiocarcinoma, and in 2 (5.6%) of 36 specimens of adjacent normal tissues. DAPK mRNA was not expressed in tumor and adjacent tissues with hypermethylation of the DAPK promoter. There were no statistical differences in the extent of differentiation and invasion, lymph node metastasis or pathologic type between the methylated and unmethylated tissues.
CONCLUSIONS: The frequency of DAPK gene methylation in cholangiocarcinoma is high and it may offer an effective means for earlier auxiliary diagnosis of the malignancy. The DAPK gene is probably suppressed by methylation, and it could become resistant to apoptosis and immunological surveillance. The DAPK gene epigenetically affected by methylation may be associated with the carcinogenesis of cholangiocarcinoma.
[1]Qingdao Univ, Coll Med, Yantai Yuhuangding Hosp, Dept Hepatobiliary Surg, Yantai 264000, Peoples R China.
[2]China Med Univ, Affiliated Hosp 1, Dept Gen Surg, Shenyang 110001, Peoples R China.
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