2. Academic Validation
  3. Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy

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

  • Dev Cell. 2021 Sep 13;56(17):2440-2454.e6. doi: 10.1016/j.devcel.2021.07.006.
Marica Rosaria Ippolito 1,  Valentino Martis 1,  Sara Martin 1,  Andréa E Tijhuis 2,  Christy Hong 2,  René Wardenaar 2,  Marie Dumont 3,  Johanna Zerbib 4,  Diana C J Spierings 2,  Daniele Fachinetti 3,  Uri Ben-David 4,  Floris Foijer 2,  Stefano Santaguida 5
Affiliations

Affiliations

  • 1 Department of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139 Milan, Italy.
  • 2 European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, the Netherlands.
  • 3 Institut Curie, PSL Research University, CNRS, UMR144, Paris, France.
  • 4 Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • 5 Department of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139 Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Via Santa Sofia 9/1, 20122 Milan, Italy. Electronic address: stefano.santaguida@ieo.it.
PMID: 34352223 DOI: 10.1016/j.devcel.2021.07.006
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.

Keywords

aneuploidy; cancer; chemotherapy; drug resistance; genome instability.

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