Methylation of GST-P-positive tongue preneoplastic lesions

在2006年，我们确定了rasH 2小鼠中4-硝基喹啉1-氧化物诱导的舌发育不良、乳头状瘤和鳞状细胞癌中p14、p16、Apc、GSTP和细胞周期蛋白D2基因的DNA甲基化谱。我们在舌癌发生过程中观察到这些基因不同的甲基化谱。在2007年，我们调查了存在的神话化在舌不典型增生病变（n=50）和鳞状细胞癌（n=24）是阳性（25不典型增生和12癌）或阴性（25不典型增生和12癌）的GSTP免疫组化使用甲基化特异性PCR。GST-P阳性异型增生中p16、p15、p14、ATM和GST-P1基因甲基化率分别为42%、58%、37%、35%和24%，GST-P阴性异型增生中为31%、29%、31%、28%和10%。GST-P阳性组p16、p15、p14、ATM、GST-1基因甲基化率分别为50%、67%、52%、68%、40%，GST-P阴性组分别为33%、31%、40%、24%、19%。我们的研究结果表明，GST-P阳性的发育不良可能是舌恶性肿瘤的直接前驱病变，并且某些功能细胞生长和凋亡的基因以及与解毒相关的基因的超甲基化参与了舌癌的发生。

In 2006, we determined DNA methyaltion profiles of p14, p16, Apc, GSTP, and cyclin D2 genes in tongue dysplasias, papillomas, and squamous cell carcinomas induced by 4-nitroquinoline 1-oxide in rasH2 mice. We observed different methylation profiles in these genes during tongue carcinogenesis. Especially the rates of hypermethylation of Apc and cyclin D2 increased during the carcinogenesis.In 2007, we investigated the presence of mythylation in the tongue dysplastic lesions (n=50) and squamous cell carcinoma(n=24) that are positive (25 dysplasias and 12 carcinomas) or negative (25 dysplasias and 12 carcinomas) for GSTP immunohistochemistry using methylation-specific PCR. The rates of hypermethylation of p16, p15, p14, ATM, and GSTP1 were 42%, 58%, 37%, 35%, 24% in the GST-P-positive dysplasia and 31%, 29%, 31%, 28%, 10% in the GSTP-negative dysplasia. Also, we observed that the rates of hypermethylation of p16, p15, p14, ATM, and GSTP1 were 50%, 67%, 52%, 68%, 40% in the GST-P-positive carcinoma and 33%, 31%, 40%, 24%, 19% in the GSTP-negative carcinoma. Our findings suggest that dysplasias positive for GST-P might be direct precursor lesions for tongue malignancy and that hypermethylation in certain genes functioning cell growth and apoptosis and those related to detoxification is involved in tongue carcinogenesis.