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

Marica Rosaria Ippolito, Valentino Martis, Sara Martin, Andréa E. Tijhuis, Christy Hong, René Wardenaar, Marie Dumont, Johanna Zerbib, Diana C. J. Spierings, Daniele Fachinetti, Uri Ben-David, Floris Foijer, Stefano Santaguida*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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 languageEnglish
Pages (from-to)2440-2454
Number of pages21
JournalDevelopmental Cell
Volume56
Issue number17
DOIs
Publication statusPublished - 13-Sep-2021

Keywords

  • TOPOISOMERASE-I INHIBITORS
  • MIS-SEGREGATION
  • SPINDLE CHECKPOINT
  • DRUG-RESISTANCE
  • FRAMEWORK
  • PROTEOME
  • CELLS
  • PROLIFERATION
  • PACLITAXEL
  • DISCOVERY

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