Abstract
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.
Original language | English |
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Pages (from-to) | 2440-2454.e6 |
Journal | Developmental Cell |
Volume | 56 |
Issue number | 17 |
DOIs | |
State | Published - 13 Sep 2021 |
Keywords
- aneuploidy
- cancer
- chemotherapy
- drug resistance
- genome instability