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

抑癌基因表达的表观遗传调控在肿瘤的发生发展中起着重要作用。基因启动子的DNA甲基化是表观遗传调控的主要途径，但其在皮肤肿瘤中的细节还没有得到很好的研究。通过我们最近建立的非同位素胞嘧啶延伸实验，我们证明了恶性黑色素瘤与良性黑素细胞痣相比，表现出CpG岛特异性的甲基化。此外，鳞状细胞癌和基底细胞癌显示CpG岛特异性低甲基化。甲基化特异性聚合酶链式反应在70%的鳞癌和30%的基底细胞癌或黑色素瘤中发现p16启动子甲基化。少数鳞癌组织中存在p14启动子甲基化。E-钙粘素启动子甲基化是最普遍的现象；在所有鳞癌中，只有基底细胞癌和黑色素瘤的一半。启动子DNA甲基化可能在皮肤肿瘤的发展中起重要作用。

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.