High frequency of promoter hypermethylation of the death-associated protein-kinase gene in nasopharyngeal carcinoma and its detection in the peripheral blood of patients.
OBJECTIVE
Death-associated protein (DAP)-kinase gene is frequently inactivated by promoter hypermethylation in cancer. The aim of this study was to evaluate the promoter methylation status of the DAP-kinase gene in nasopharyngeal carcinoma (NPC).


METHODS
The methylation status was evaluated by methylation-specific PCR (MSP). Thirty-two NPC biopsy specimens, plasma and buffy coat of 12 patients, 5 NPC cell lines, 3 normal nasopharyngeal biopsy tissues, and 2 normal nasopharyngeal epithelial primary cultures were included in this study.


RESULTS
There was no promoter hypermethylation in all 3 normal nasopharyngeal tissues and 2 normal nasopharyngeal primary cultures. Hypermethylation was found in 24 (75%) NPC primary tumor biopsies and 4 (80%) NPC cell lines. Of the 24 patients with hypermethylation of DAP-kinase promoter in the primary tumors, 12 patients had their plasma and buffy coat DNA available for MSP study. Hypermethylated DAP-kinase promoter was detectable in 5 patients in the plasma but not in the buffy coat, 2 patients in the buffy coat but not in the plasma, and 1 patient in both plasma and buffy coat. Four patients had no detectable hypermethylated DAP-kinase promoter in both plasma and buffy coat. Hypermethylation of DAP-kinase promoter was found in both early- and late-stage NPC.


CONCLUSIONS
Our results show that hypermethylation of the DAP-kinase promoter is a common early event in NPC. The high frequency of identification of hypermethylated DAP-kinase promoter in plasma and buffy coat of NPC patients illustrates its potential clinical application as tumor marker for the diagnosis and monitoring of treatment result.
Wong
Thian Sze
TS
Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, SAR China.
Chang
Hsiao Wen
HW
Tang
Kwong Chi
KC
Wei
William Ignace
WI
Kwong
Dora Lai Wen
DL
Sham
Jonathan Shun Tong
JS
Yuen
Anthony Po Wing
AP
Kwong
Yok Lam
YL
D051017:Apoptosis Regulatory Proteins; D001706:Biopsy; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics*; D002277:Carcinoma / Q000097:blood / Q000201:enzymology*; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D005260:Female; D006801:Humans; D008297:Male; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000201:enzymology*; D011401:Promoter Regions, Genetic; D013447:Sulfites / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D013447:Sulfites; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases