Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy

Summary Mitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations chromosome copy number induce wide variety cellular stresses, including genome instability. Here, we show that cells might exploit aneuploidy-induced instability and the resulting gene copy-number changes survive under conditions selective pressure, such as chemotherapy. Resistance chemotherapeutic drugs was dictated by acquisition recurrent karyotypes, indicating dosage play role driving chemoresistance. Thus, our study establishes causal link between aneuploidy-driven chemoresistance explain why some chemotherapies fail succeed.