表观基因组变化定义了婴儿期致命的CIMP阳性表观瘤
11] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Division of Neurosurgery, University of Toronto, Toronto, Ontario M5S 1A8, Canada [4].
后脑表膜瘤是一种常见的儿童大脑瘤,表现出很少的遗传突变,但表现出表观遗传变化. 针对这些表观遗传改变为这种恶性瘤提供了一个有前途的新治疗策略.
科学领域:
- 神经瘤学神经瘤学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 儿科瘤学 儿科瘤学
背景情况:
- 膜瘤是儿童常见的大脑瘤,主要影响后脑.
- 目前的治疗方法 (手术,辐射) 缺乏化学疗法的有效性.
研究的目的:
- 调查后脑表膜瘤的遗传和表观遗传特征.
- 确定预后不佳病例的潜在治疗点.
主要方法:
- 全基因组和全外基因组测序47个后脑内膜瘤.
- 对CpG岛屿甲基化剂表型 (CIMP) 的分析.
- 评估Polycomb镇压复合体2 (PRC2) 的目标和H3K27三甲基化.
主要成果:
- 后脑端膜瘤显示出异常低的突变率,没有显著的复发性体质单核酸变异.
- 预后不佳的瘤表现出一种CpG岛甲基器表型 (CIMP).
- 表观遗传沉默点多镇压复合体2 (PRC2) 点,通过H3K27三甲基化影响差异化基因.
结论:
- 表观遗传失调,特别是CIMP和PRC2通路的改变,是后脑尾瘤的关键驱动因素.
- 阳性CIMP瘤对向DNA或H3K27甲基化的药物敏感.
- 表观遗传修饰剂代表了这种致命的儿科大脑恶性瘤的合理治疗候选者.
更多相关视频
08:22A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Published on: December 1, 2017
10:13Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice
Published on: August 12, 2014
相关概念视频
Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
Epigenetic Regulation
X-chromosome...
Epigenetic Regulation
