新突变的目标是脑髓母细胞瘤的不同亚组
Giles Robinson1, Matthew Parker, Tanya A Kranenburg
1St Jude Children's Research Hospital, Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA.
Nature
|June 23, 2012
概括
这项研究发现了新的基因突变驱动脑髓母细胞瘤,一个儿童大脑瘤. 这些发现揭示了不同脑髓母细胞瘤亚组中明显的表观遗传变化,提供了潜在的治疗点.
科学领域:
- 基因组学就是基因组学.
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 脑膜母细胞瘤是一种恶性儿童大脑瘤,具有四个不同的分子子组.
- 了解脑髓母细胞瘤的遗传驱动因素对于开发向疗法至关重要.
研究的目的:
- 为了确定驱动脑髓母细胞瘤在其子组中的发展的新型体质突变.
- 调查表观遗传机制改变在脑髓母细胞瘤发病过程中的作用.
主要方法:
- 37个脑髓母细胞瘤瘤的全基因组测序与正常血液相匹配.
- 在另外56个脑髓母细胞瘤中对136个基因进行了向测序.
- 在WNT子组脑髓母细胞瘤的老鼠前代突变的体内建模.
主要成果:
- 在41个以前未被描述的基因中确定了反复发生的突变.
- 发现了特定于子组的表观遗传变化,包括H3K27和H3K4三甲基化 (例如KDM6A,ZMYM3) 的调节者,在第3和第4个子组.
- 在WNT亚组瘤中发现CTNNB1相关的染色质重塑剂 (例如,SMARCA4,CREBBP).
- 鼠标模型揭示了维持细胞系 (DDX3X) 和启动/合作瘤发生的基因 (CDH1,PIK3CA).
结论:
- 这项研究提供了对脑髓母细胞瘤亚群的分子病变产生有意义的见解.
- 确定了脑髓母细胞瘤的新型遗传驱动因素和治疗点,特别关注表观遗传调节剂.
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