DNA methylation of tumor suppressor gene in the development and in the metastasis of skin cancers

肿瘤抑制基因表达的表观遗传调控在肿瘤发生发展中起重要作用。基因启动子区DNA甲基化是表观遗传调控的一个重要途径，但在皮肤肿瘤中的甲基化研究还不多，本研究利用新近建立的非同位素胞嘧啶延伸法，证实了恶性黑色素瘤与良性黑色素细胞痣相比存在CpG岛特异性甲基化。甲基化特异性PCR显示70%的SCC、30%的BCC和黑色素瘤中p16基因启动子甲基化。p14基因启动子甲基化在少数SCC中存在。E-cadherin基因启动子甲基化是最常见的，在所有的SCC病例中，BCC和黑素瘤病例的一半。启动子DNA甲基化可能在皮肤肿瘤的发生中起重要作用。

Epigenetic regulation of the expression of tumor suppressor genes plays important role in tumor development. DNA methylation of gene promoter is a major pathway of the epigenetic regulation, however, its detail has not well studied in skin neoplasms.With the power of non-isotopic cytosine extension assay, which we established recently, we demonstrated that malignant melanoma showed CpG-island specific hypermethylation compared with benign melanocytic nevus. Also, squamous cell carcinoma and basal cell carcinoma revealed CpG-island-specific hypomethylation.Methylation-specific PCR revealed p16 promoter methylation in 70% of SCC, and 30% of BCC or melanoma. p14 promoter methylation was observed in small number of SCC. E-cadherin promoter methylation was most ubiquitously observed; in all the cases of SCC, halves the cases of BCC and melanoma.Promoter DNA methylation may play an important role in the development of skin neoplasms.