Promoter hypermethylation of death-associated protein kinase gene in cholangiocarcinoma.
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.
Liu
Xiao-Fang
XF
Department of Hepatobiliary Surgery, Yantai Yuhuangding Hospital, Medical College of Qingdao University, Yantai 264000, China. Liu634@263.net
Kong
Fan-Min
FM
Xu
Zheng
Z
Yu
Shao-Ping
SP
Sun
Fu-Bo
FB
Zhang
Cui-Sheng
CS
Huang
Qing-Xian
QX
Zhou
Xian-Ting
XT
Song
Zhan-Wen
ZW
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000502:physiology*; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000502:physiology*; D002147:Calmodulin / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000235:genetics*; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013447:Sulfites / Q000737:chemistry
D051017:Apoptosis Regulatory Proteins; D002147:Calmodulin; D013447:Sulfites; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C009279:sodium bisulfite