title: Aberrant DNA methylation of tumor-related genes in oral rinse: a noninvasive method for detection of oral squamous cell carcinoma.
abstract: BACKGROUND
  The early detection of oral squamous cell carcinoma (OSCC) is important, and a screening test with high sensitivity and specificity is urgently needed. Therefore, in this study, the authors investigated the methylation status of tumor-related genes with the objective of establishing a noninvasive method for the detection of OSCC.
  
  
  METHODS
  Oral rinse samples were obtained from 34 patients with OSCC and from 24 healthy individuals (controls). The methylation status of 13 genes was determined by using methylation-specific polymerase chain reaction analysis and was quantified using a microchip electrophoresis system. Promoter methylation in each participant was screened by receiver operating characteristic analysis, and the utility of each gene's methylation status, alone and in combination with other genes, was evaluated as a tool for oral cancer detection.
  
  
  RESULTS
  Eight of the 13 genes had significantly higher levels of DNA methylation in samples from patients with OSCC than in controls. The genes E-cadherin (ECAD), transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2), retinoic acid receptor beta (RARβ), and O-6 methylguanine DNA methyltransferase (MGMT) had high sensitivity (>75%) and specificity for the detection of oral cancer. OSCC was detected with 100% sensitivity and 87.5% specificity using a combination of ECAD, TMEFF2, RARβ, and MGMT and with 97.1% sensitivity and 91.7% specificity using a combination of ECAD, TMEFF2, and MGMT.
  
  
  CONCLUSIONS
  The aberrant methylation of a combination of marker genes present in oral rinse samples was used to detect OSCC with >90% sensitivity and specificity. The detection of methylated marker genes from oral rinse samples has great potential for the noninvasive detection of OSCC.
authors.affiliation: Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagata
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Hamada
authors.forename: Norishige
authors.initials: N
authors.lastname: Yamada
authors.forename: Seiya
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Sho
authors.initials: S
authors.lastname: Kitamoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kanmura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nomura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kamikawa
authors.forename: Suguru
authors.initials: S
authors.lastname: Yonezawa
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics*; D019175:DNA Methylation; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012463:Saliva / Q000737:chemistry*; D012680:Sensitivity and Specificity