Aberrant promoter hypermethylation of p16 and MGMT genes in oral squamous cell carcinomas and the surrounding normal mucosa

J Cancer Res Clin Oncol. 2006 Nov;132(11):735-43. doi: 10.1007/s00432-006-0122-8. Epub 2006 Jun 22.

Abstract

Purpose: 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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / metabolism
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Verrucous / genetics
  • Carcinoma, Verrucous / metabolism
  • Case-Control Studies
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • DNA / genetics
  • DNA Methylation*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mouth Mucosa / metabolism
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / metabolism
  • O(6)-Methylguanine-DNA Methyltransferase / genetics*
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / genetics*
  • Risk Factors

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA
  • O(6)-Methylguanine-DNA Methyltransferase