没有驱动基因的肺腺癌通过不同的遗传,表观遗传和利基结构进化途径汇聚到共同的适应策略
Robert A Gatenby1, Kimberly A Luddy2, Jamie K Teer2,3
1Department of Cancer Biology and Evolution, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA. Robert.gatenby@moffitt.org.
癌细胞发展出融合的策略,失去分化和细胞相互作用. 选择的突变通常会加强表观遗传变化,推动肺腺癌的适应.
科学领域:
- 在瘤学瘤学.
- 进化生物学 进化生物学
- 基因组学就是基因组学.
背景情况:
- 癌细胞表现出分子异质性,但可能共享适应性策略.
- 了解瘤的融合进化可以揭示共同的选择力.
研究的目的:
- 为了研究没有常见的驱动基因的肺腺癌中的基因突变和表达变化.
- 为了确定由表观遗传和遗传选择驱动的融合适应性策略.
主要方法:
- 在313个肺腺癌中对基因突变和表达的系统分析.
- 确定积极选择的突变和差异表达的基因.
主要成果:
- 376个非同义突变显示出积极的进化选择.
- 观察到基因表达的显著变化,有1736个基因上调和2430个基因下调.
- 选择的突变往往"硬化"了先前存在的表观遗传适应.
- 融合的LUAD表型涉及到差异化的功能和细胞-细胞相互作用的损失.
- 上调的基因与细胞周期,DNA修复,p53通路,表观遗传修饰剂和新陈代谢有关.
- 离子通道的下调表明,降低的跨膜潜力有助于增殖.
- 利基建筑涉及创建一个硬的,免疫抑制的微环境.
结论:
- 没有正规驱动因素的肺腺癌通过相互连接的遗传,表观遗传和生态途径演变为融合的表型.
- 适应性策略涉及正常组织功能和利基结构的损失.
- 选择的基因对正常细胞功能和癌细胞适应性都至关重要.
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