Aberrant promoter hypermethylation of p16 and MGMT genes in oral squamous cell carcinomas and the surrounding normal mucosa.
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.
Kato
Keizo
K
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
Hara
Akira
A
Kuno
Toshiya
T
Mori
Hideki
H
Yamashita
Tomomi
T
Toida
Makoto
M
Shibata
Toshiyuki
T
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
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004247:DNA; D019853:O(6)-Methylguanine-DNA Methyltransferase