Department of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139 Milan, Italy.
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, the Netherlands.
Dev Cell. 2021 Sep 13;56(17):2440-2454.e6. doi: 10.1016/j.devcel.2021.07.006. Epub 2021 Aug 4.
Mitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability and the resulting gene copy-number changes to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven changes in gene copy number and chemoresistance and might explain why some chemotherapies fail to succeed.
有丝分裂错误导致非整倍体，即染色体组不平衡的一种情况，在癌细胞中经常发现。染色体拷贝数的改变会引起多种细胞应激，包括基因组不稳定。在这里，我们表明癌细胞可能利用非整倍体诱导的基因组不稳定性和由此产生的基因拷贝数变化，在选择性压力下生存，如化疗。对化疗药物的耐药性是由反复出现的核型获得决定的，这表明基因剂量可能在驱动化疗耐药性方面发挥作用。因此，我们的研究在非整倍体驱动的基因拷贝数变化与化疗耐药性之间建立了因果关系，并可能解释为什么某些化疗药物未能成功。
