对癌症表观基因组学的分子病理学方法及其临床应用
1Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Pathology international
|March 14, 2024
概括
DNA甲基化变化是癌症发展的早期指标,即使在癌前组织中也是如此. 这些由炎症和病毒感染等因素驱动的表观遗传变化,有助于多阶段癌症发生,并可以作为诊断生物标志物.
科学领域:
- 表观遗传学和分子瘤学
- 癌症基因组学和生物标志物发现发现
背景情况:
- 多个阶段的致癌症包括组织结构,细胞粘附和极性中断.
- 卡德林-卡宁系统,特别是E-卡德林 (CDH1),与DNA甲基化沉默瘤抑制基因有关.
- 表观遗传学机制,特别是DNA甲基化,在癌症发生过程中一直没有得到充分的研究,直到20世纪90年代.
研究的目的:
- 研究表观遗传学机制,特别是DNA甲基化在多阶段癌症发生中的作用.
- 确定癌前组织中的DNA甲基化异常及其对癌症发展的贡献.
- 开发基于DNA甲基化概况的诊断标记物和治疗点.
主要方法:
- 显微镜组织病理学观察和分子病理学分析.
- 调查慢性肝炎,肝硬化和癌前组织中的DNA甲基化异常.
- 对异常DNA甲基转移酶 (DNMT1,DNMT3B) 表达和拼接的分析.
- 在细胞癌中识别CpG岛屿甲基化剂表型,使用多层欧米克分析.
- 澄清与非酒精性脂肪肝炎 (NASH) 相关的肝细胞癌中的DNA甲基化概况.
主要成果:
- 在癌前疾病,如慢性肝炎和肝硬化中,DNA甲基化异常常见.
- DNA甲基转移酶的异常表达有助于DNA甲基化变化.
- 在细胞癌中发现了CpG岛屿甲基化剂表型;发现了治疗点.
- 阐明了与NASH相关的肝细胞癌的DNA甲基化概况.
- 对于NASH癌症发生风险和上泌尿道癌症的诊断标志物开发.
- 创建了基于液态色谱的高性能DNA甲基化诊断系统.
结论:
- DNA甲基化变化发生在癌症发生的早期,受炎症,吸烟和病毒感染等因素的影响.
- 这些表观遗传变化有助于癌症的发展,基因表达和基因组不稳定.
- 在癌症中,DNA甲基化变化是遗传的/增强的,影响了攻击性和患者的结果.
- 基因甲基化改变作为诊断,预防和预防性医学的宝贵生物标志物.
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