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

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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.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Sciences, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan

    Keizo Kato, Tomomi Yamashita, Makoto Toida & Toshiyuki Shibata

  2. Department of Tumor Pathology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan

    Akira Hara, Toshiya Kuno & Hideki Mori

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  1. Keizo Kato
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  2. Akira Hara
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  3. Toshiya Kuno
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  5. Tomomi Yamashita
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  7. Toshiyuki Shibata
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Correspondence to Keizo Kato.

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Kato, K., Hara, A., Kuno, T. et al. Aberrant promoter hypermethylation of p16 and MGMT genes in oral squamous cell carcinomas and the surrounding normal mucosa. J Cancer Res Clin Oncol 132, 735–743 (2006). https://doi.org/10.1007/s00432-006-0122-8

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  • DOI: https://doi.org/10.1007/s00432-006-0122-8

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