癌症基因组图谱中的癌症信号通路
Francisco Sanchez-Vega1, Marco Mina2, Joshua Armenia1
1Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cell
|April 7, 2018
概括
癌细胞经常改变关键的信号通路. 这项研究分析了9125种瘤,发现89%的瘤有驱动性变化,57%的瘤有可向性变化,显示了组合治疗的潜力.
科学领域:
- 癌症学
- 基因组学
- 分子生物学
背景情况:
- 细胞周期的基因变化,细胞亡和生长途径是癌症的标志.
- 这些变化的具体机制和同时发生在不同瘤类型和个体瘤中存在显著差异.
研究的目的:
- 综合分析不同癌症类型的十种规范信号通路的体质变化.
- 确定这些路径变化的共发生和相互排他性的模式.
- 评估潜在治疗策略的可向变化的瘤比例.
主要方法:
- 利用来自癌症基因组图谱 (TCGA) 的9125个瘤的多基因数据 (突变,拷贝数,mRNA表达,基因融合,DNA甲基化).
- 分析了十个关键癌症相关途径的变化:细胞周期,Hippo,Myc,Notch,Nrf2,PI-3- 激酶/ Akt,RTK- RAS,TGFβ信号传递,p53,和β- 素/ Wnt.
- 对33种癌症和64种亚型进行分层分析.
主要成果:
- 在分析的瘤中,有89%的瘤表现出至少在这十个路径中的一个驱动性变化.
- 在57%的瘤中,至少有一种可能被现有药物向的变化.
- 三成的瘤显示多个可向的变化,
结论:
- 在癌症中,常规信号通路被普遍改变,具体模式因瘤类型而异.
- 很大一部分瘤具有可向的变化,突出了精准医学和组合治疗策略的机会.
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