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，这是一种核型失衡的情况，经常在癌细胞中发现。染色体拷贝数的改变会引起多种细胞应激，包括基因组不稳定性。在这里，我们展示了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（如化疗）条件下存活。对化疗药物的耐药性取决于反复核型的获得，这表明基因剂量可能在驱动化学耐药性中发挥作用。因此，我们的研究建立了非整倍体驱动的基因拷贝数变化与化学抗性之间的因果关系，并可能解释为什么某些化学疗法未能成功。