title: Promoter hypermethylation of high-in-normal 1 gene in primary nasopharyngeal carcinoma.
abstract: OBJECTIVE
  The methylation of high-in-normal-1 (HIN-1) gene promoter in undifferentiated nasopharyngeal carcinoma (NPC) is studied.
  
  
  METHODS
  The methylation status of HIN-1 in NPC cell lines, primary NPC, paired nasopharyngeal swabs, paired throat-rinsing fluid, and paired peripheral blood was assessed by methylation-specific PCR assay. The relationship between HIN-1 promoter methylation and transcription in NPC cell lines was evaluated by reverse transcription-PCR and demethylation agent treatment (5-aza-2-deoxycytidine).
  
  
  RESULTS
  Hypermethylated promoter was observed in five of five (100%) NPC cell lines and not found in three normal nasopharyngeal outgrowths, two tonsil epithelial cell cultures, and two skin fibroblast cultures. Reverse transcription-PCR assay indicated that HIN-1 transcription was significantly down-regulated in the NPC cell line with promoter methylation. Treatment with demethylation agent, 5-aza-2-deoxycytidine, restored HIN-1 transcription in the NPC cell line. Methylated HIN-1 promoter was found in 36 of 47 (77%) primary NPC tumors and not found in the normal nasopharyngeal biopsies. Methylated HIN-1 promoter was detected in 12 of 26 (46%) nasopharyngeal swabs, 5 of 26 (19%) throat-rinsing fluids, 2 of 11 (18%) plasmas, and 5 of 11 (46%) buffy coats of peripheral blood of the NPC patients but was not detectable in all normal controls.
  
  
  CONCLUSIONS
  HIN-1 promoter hypermethylation is common in NPC. Methylated promoter DNA in nasopharyngeal swab, throat-rinsing fluid, and peripheral blood might be potentially useful as tumor marker for screening of NPC.
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR China.
authors.forename: Thian Sze
authors.initials: TS
authors.lastname: Wong
authors.forename: Dora Lai-Wen
authors.initials: DL
authors.lastname: Kwong
authors.forename: Jonathan Shun-Tong
authors.initials: JS
authors.lastname: Sham
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: William Ignace
authors.initials: WI
authors.lastname: Wei
authors.forename: Yok Lam
authors.initials: YL
authors.lastname: Kwong
authors.forename: Anthony Po-Wing
authors.initials: AP
authors.lastname: Yuen
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D002454:Cell Differentiation; D016207:Cytokines / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; C434732:SCGB3A1 protein, human; D025521:Tumor Suppressor Proteins