title: Promoter hypermethylation of tumor suppressor genes in serum as potential biomarker for the diagnosis of nasopharyngeal carcinoma.
abstract: OBJECTIVE
  Promoter hypermethylation of tumor suppressor genes may serve as a promising biomarker for the diagnosis of cancer. Cell-free circulating DNA (cf-DNA) shares hypermethylation status with primary tumors. This study investigated promoter hypermethylation of five tumor suppressor genes as markers in the detection of nasopharyngeal carcinoma (NPC) in serum samples.
  
  
  METHODS
  cf-DNA was extracted from serum collected from 40 NPC patients and 41 age- and sex-matched healthy subjects. The promoter hypermethylation status of the five genes (RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1) was assessed by methylation-specific PCR after sodium bisulfite conversion. Differences in the methylation status of these five genes between NPC patients and healthy subjects were compared.
  
  
  RESULTS
  The concentration of cf-DNA in the serum of NPC patients was significantly higher than that in normal controls. The five tumor suppressor genes - RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1 - were found to be methylated in 17.5%, 22.5%, 25.0%, 51.4% and 64.9% of patients, respectively. The combination of four-gene marker - CDKN2A, DLEC1, DAPK1 and UCHL1 - had the highest sensitivity and specificity in predicting NPC.
  
  
  CONCLUSIONS
  Screening DNA hypermethylation of tumor suppressor genes in serum was a promising approach for the diagnosis of NPC.
authors.affiliation: Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. fangyun.tian@connect.polyu.hk
authors.forename: Fangyun
authors.initials: F
authors.lastname: Tian
authors.forename: Shea Ping
authors.initials: SP
authors.lastname: Yip
authors.forename: Dora Lai Wan
authors.initials: DL
authors.lastname: Kwong
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Lin
authors.forename: Zhining
authors.initials: Z
authors.lastname: Yang
authors.forename: Vincent Wing Cheung
authors.initials: VW
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics*; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D064550:Death-Associated Protein Kinases / Q000097:blood / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000235:genetics / Q000821:virology; D005260:Female; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D009360:Neoplastic Cells, Circulating; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000097:blood / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000097:blood / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C119064:DLEC1 protein, human; D004273:DNA, Neoplasm; D004279:DNA, Viral; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C482860:UCHL1 protein, human; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D043222:Ubiquitin Thiolesterase
keywords: Cell-free circulating DNA; DNA hypermethylation; Diagnosis; MSP; Nasopharyngeal carcinoma; Tumor suppressor genes