title: Aberrant promoter hypermethylation of p16 and MGMT genes in oral squamous cell carcinomas and the surrounding normal mucosa.
abstract: OBJECTIVE
  Several genetic alterations have been reported to contribute to the development of oral squamous cell carcinoma (OSCC). Recent studies have shown roles of promoter hypermethylation of tumor suppressor genes, including p16 and MGMT, in several types of cancers. The purpose of this study is to examine the hypermethylation status of p16 and MGMT genes in both oral cancers and normal mucosa, surrounding the cancers.
  
  
  METHODS
  Promoter hypermethylation status of p16 and MGMT genes were examined by the methylation-specific PCR (MSP) in OSCC (n = 51), verrucous carcinoma (n = 2), and carcinoma in situ (n = 2) tissues. Moreover, normal mucosa surrounding the cancers were also examined in 22 cases out of the 51 OSCCs. As a normal control, oral mucosa from healthy volunteers (n = 18) was used.
  
  
  RESULTS
  Aberrant promoter hypermethylation of p16 and MGMT genes was detected in 50.9% (28 of 55) and 56.4% (31 of 55) of the total malignant cases, respectively. As for the 22 OSCC cases, in which paired cancerous tissues and the surrounding normal mucosa were examined simultaneously, promoter hypermethylation of p16 and MGMT genes was confirmed in 72.73% (16 of 22) and 68.18% (15 of 22), respectively. In contrast, as for the surrounding normal mucosa, promoter hypermethylation of p16 and MGMT genes was recognized in 27.27% (6 of 22) cases and 40.91% (9 of 22), respectively.
  
  
  CONCLUSIONS
  Hypermethylation of both p16 and MGMT genes was frequently detected in not only OSCC tissues, but also the surrounding normal mucosa around the cancerous tissues. Thus promoter hypermethylation of p16 and MGMT genes are an important, probably early event in oral carcinogenesis.
authors.affiliation: Department of Oral and Maxillofacial Sciences, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan. keizo@cc.gifu-u.ac.jp
authors.forename: Keizo
authors.initials: K
authors.lastname: Kato
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kuno
authors.forename: Hideki
authors.initials: H
authors.lastname: Mori
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamashita
authors.forename: Makoto
authors.initials: M
authors.lastname: Toida
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shibata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D018289:Carcinoma, Verrucous / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004247:DNA; D019853:O(6)-Methylguanine-DNA Methyltransferase