The research for the classification by molecular biology and the development of a novel therapy in squamous cell carcinomas of the skin

皮肤鳞状细胞癌的分子生物学分类研究及新疗法的开发

• 批准号: 15591180
• 负责人: KUBO Yoshiaki
• 金额: $ 1.79万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591180/
• 关键词: squamous cell carcinoma(SCC); Promoter hypermethylation; cancer-related genes; E-cadherin; p16^<INK4a>; pRb; MGMT; RIZ1; PTEN; p14^<ARF>; p15; p16^<INK4a>

Squamous cell carcinomas (SCCs) of the skin are supposed to develop through the multistep process that involves activation of proto-oncogenes and/or inactivation of tumor suppressor genes in the human skin keratinocytes. Recently, in addition to gene mutations and chromosomal abnormalities, epigenetic inactivation due to aberrant DNA promoter methylation of cancer-related genes has been revealed to be a common and important feature of several cancers. In this study, we analyzed promoter methylation status of E-cadherin, p16^<INK4a>, p14^<ARF>, p15, pRb, DAPK, MGMT, RASSF1A, RIZ1, and PTEN by means of bisulfite PCR using DNA samples from 20 cases of SCCs of the skin. Promoter methylation was detected in 19/20 (95%), 4/20 (20%), 3/20 (15%), 1/20 (5%), 1/20 (5%), 3/20 (15%), 3/20 (15%), 1/20 (5%), 0/20 (0%), and 0/20 (0%), respectively. These findings indicate that epigenetic inactivation of cancer-related genes might be a common feature of SCCs of the skin and have some relevance to the carcinogenesis in SCCs of the skin.

皮肤的鳞状细胞癌（SCC）应该通过多步过程发展，涉及人类皮肤角质形成细胞中肿瘤抑制基因的激活和/或失活。最近，除了基因突变和染色体异常外，由于异常的DNA启动子甲基化引起的癌症相关基因的表观遗传失活是几种癌症的常见和重要特征。在这项研究中，我们分析了E-钙粘蛋白，p16^<ink4a>，p14^<ARF>，p15，prb，dapk，mgmt，mgmt，rassf1a，riz1和pten的启动子甲基化状态，该状态是使用Bisulfite PCR使用SCCS的20例SCCS的DNA样本的。在19/20（95％），4/20（20％），3/20（15％），1/20（5％），1/20（5％），3/20（15％），3/20（15％），3/20（15％），1/20（5％），1/20（5％），0/20（0％），0/20（0％）和0/20（0％）中检测到启动子甲基化。这些发现表明，与癌症相关的基因的表观遗传失活可能是皮肤SCC的常见特征，并且与皮肤SCC中的致癌作用有一定程度。