title: High frequency of promoter hypermethylation of the death-associated protein-kinase gene in nasopharyngeal carcinoma and its detection in the peripheral blood of patients.
abstract: 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.
authors.affiliation: Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, SAR China.
authors.forename: Thian Sze
authors.initials: TS
authors.lastname: Wong
authors.forename: Hsiao Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Kwong Chi
authors.initials: KC
authors.lastname: Tang
authors.forename: William Ignace
authors.initials: WI
authors.lastname: Wei
authors.forename: Dora Lai Wen
authors.initials: DL
authors.lastname: Kwong
authors.forename: Jonathan Shun Tong
authors.initials: JS
authors.lastname: Sham
authors.forename: Anthony Po Wing
authors.initials: AP
authors.lastname: Yuen
authors.forename: Yok Lam
authors.initials: YL
authors.lastname: Kwong
mesh_terms: 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
chemical_list: D051017:Apoptosis Regulatory Proteins; D013447:Sulfites; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases