Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands; These authors made an equal contribution to this work.
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands; These authors made an equal contribution to this work.
Trends Genet. 2019 Apr;35(4):279-291. doi: 10.1016/j.tig.2019.01.003. Epub 2019 Feb 8.
Chromosome segregation errors are an important source of genomic diversification that promote tumor heterogeneity and evolution. However, the aneuploidy induced by chromosome missegregations causes cellular stress at many levels, raising the question of how segregation errors can be tolerated in cancer. Additionally, we now know that chromosome segregation errors can lead to activation of the innate immune system, producing yet another challenge for chromosomally unstable cells. These observations imply that several liabilities are encountered during tumor evolution, which could potentially be exploited for cancer therapies. Here, we provide an overview of the different causes of segregation errors, their impact on cellular and genomic homeostasis, and discuss recent studies that help to understand how tolerance towards imbalanced karyotypes can be obtained.
染色体分离错误是基因组多样化的一个重要来源，可促进肿瘤异质性和进化。然而，染色体错误分离导致的非整倍体在多个层面上引起细胞应激，这就提出了一个问题，即在癌症中如何耐受分离错误。此外，我们现在知道，染色体分离错误可导致先天免疫系统的激活，这给染色体不稳定的细胞带来了另一个挑战。这些观察结果表明，在肿瘤进化过程中会遇到几种缺陷，这些缺陷可能会被用于癌症治疗。在这里，我们概述了分离错误的不同原因、它们对细胞和基因组动态平衡的影响，并讨论了有助于理解如何获得对不平衡核型的耐受性的最新研究。
