Laboratory of Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Curr Opin Genet Dev. 2020 Feb;60:41-47. doi: 10.1016/j.gde.2020.02.009. Epub 2020 Mar 6.
In the early stages of carcinogenesis cells confront two key suppressive checkpoints; senescence and telomere crisis. Telomere crisis is characterized by massive chromosomal instability and cell death. The genetic instability initiated during crisis leaves detectable scars on cancer genomes, the full scope of which is only just beginning to be appreciated. In particular, the dramatic genome reshuffling phenomenon chromothripsis has been mechanistically linked to the resolution of DNA bridges formed by dicentric chromosomes, and by the shattering of DNA inside micronuclei. Furthermore, an intriguing connection to innate immune signaling has begun to position telomere crisis as a crucial stage not only in the evolution of the cancer genome, but also in the interaction between the genome and the immune system.
在癌变的早期阶段,细胞面临两个关键的抑制检查点:衰老和端粒危机。端粒危机的特征是大量的染色体不稳定性和细胞死亡。在危机期间引发的遗传不稳定性在癌症基因组上留下了可检测的痕迹,而这些痕迹的全貌才刚刚开始被人们所认识。特别是,戏剧性的基因组重排现象——染色体重排,已经在机制上与双着丝粒染色体形成的 DNA 桥的解决以及微核内 DNA 的碎裂联系起来。此外,与先天免疫信号的有趣联系开始将端粒危机定位为不仅是癌症基因组进化的关键阶段,也是基因组与免疫系统相互作用的关键阶段。