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

皮肤癌发生和转移中抑癌基因的 DNA 甲基化

• 批准号: 13670870
• 负责人: FUJIWARA Hiroshi
• 金额: $ 2.3万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670870/
• 关键词: p16; p14; E-cadherin; malignant melanoma; squamous cell carcinoma; basal cell carcinoma; methylation; cytosine extension assay; DNA; ケラチノサイト; メラノサイト; 末梢血リンパ球

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.

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。

项目成果

Fujiwara, Hiroshi: "Non-isotopic cytosine extension assay : A highly sensitive method to evaluate CpG island methylation in the whole genome"Analytical Biochemistry. 307. 386-389 (2002)

Fujiwara, Hiroshi：“非同位素胞嘧啶延伸测定：一种评估全基因组中 CpG 岛甲基化的高度灵敏方法”分析生物化学。

Fujiwara H, Ito M: "Non-isotopic cytosine extension assay: A highly sensitive method to evaluate CpG island methylation in the whole genome"Analytical Biochemistry. 307. 386-389 (2002)

Fujiwara H、Ito M：“非同位素胞嘧啶延伸测定：一种评估全基因组中 CpG 岛甲基化的高度灵敏方法”分析生物化学。