网络攻击突变的全基因组解码重新连接癌症信号
Pau Creixell1, Erwin M Schoof1, Craig D Simpson2
1Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark.
Cell
|September 22, 2015
概括
研究人员在癌症中发现了网络攻击突变 (NAM),揭示了突变破坏细胞信号的新方式. 这一发现可能会带来更好的治疗癌症网络.
科学领域:
- 癌症学
- 分子生物学
- 生物信息学
背景情况:
- 癌细胞通过累积突变来发展异常特征, 破坏细胞信号网络.
- 对这些突变及其对信号通路的影响进行全面分析仍然是一个挑战.
研究的目的:
- 识别和描述在癌症中驱动病态表型的网络攻击突变 (NAM).
- 开发和应用用于系统分析癌症突变及其对信号网络的影响的计算工具.
主要方法:
- 开发了ReKINect,一个用于识别六种NAM的计算平台.
- 从卵巢癌细胞系和全球癌症基因组库中分析出外体和定量 () 蛋白体.
- 实验验证的已识别的NAM,包括特定的酶突变.
主要成果:
- 确定了六类NAM,包括酶/SH2调制,网络重新连接和酸化位变化.
- 发现突变分子逻辑门,转向三信号传递,
- 在癌症中发现了激酶失活热点,并验证了PKCγ M501I和PKD1 D665N等特定的NAM.
结论:
- 在复杂的癌症基因组和信号网络中有效识别功能性NAM.
- 这些发现为癌症特异性的分子逻辑提供了洞察力,并为向癌症治疗提供了潜力.
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