激活ALK中的突变可以在神经母细胞瘤中提供治疗点
Rani E George1, Takaomi Sanda, Megan Hanna
1Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|October 17, 2008
概括
在儿童癌症神经母细胞瘤中发现了ALK基因的新突变. 这些ALK突变使瘤对向ALK抑制剂敏感,提供了一种新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 神经母细胞瘤是一种致命的儿童癌症,起源于外周交感神经系统.
- 高危神经母细胞瘤经常复发,尽管进行了密集化疗,但致命.
研究的目的:
- 在神经母细胞瘤中识别新的遗传突变.
- 研究ALK基因在神经母细胞瘤发育和进展中的作用.
- 探索神经母细胞瘤的向治疗选择.
主要方法:
- 在原发性神经母细胞瘤瘤中测序ALK基因.
- 使用细胞系 (Ba/F3,神经母细胞瘤细胞系) 的功能研究.
- 对ALK抑制剂和基因淘汰的敏感性评估.
主要成果:
- 在8%的原发性神经母细胞瘤中检测到ALK基因中以前未知的突变.
- 特定的ALK突变 (F1174L,R1275Q) 在Ba/F3细胞中赋予了细胞因子独立的生长.
- 具有ALK突变的神经母细胞瘤细胞系对ALK抑制剂和诱导亡的敏感性.
结论:
- 激活ALK突变存在于神经母细胞瘤中,并驱动瘤生长.
- 向抑制ALK为神经母细胞瘤提供了一个有前途的治疗策略.
- 这一发现为开发针对这种侵袭性儿童癌症的新疗法提供了分子基础.
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