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Aneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness

Author

Listed:
  • Federica Schiavoni

    (The Institute of Cancer Research)

  • Pedro Zuazua-Villar

    (The Institute of Cancer Research)

  • Theodoros I. Roumeliotis

    (The Institute of Cancer Research)

  • Graeme Benstead-Hume

    (The Institute of Cancer Research
    University of Sussex)

  • Mercedes Pardo

    (The Institute of Cancer Research)

  • Frances M. G. Pearl

    (University of Sussex)

  • Jyoti S. Choudhary

    (The Institute of Cancer Research)

  • Jessica A. Downs

    (The Institute of Cancer Research)

Abstract

Aneuploidy results in decreased cellular fitness in many species and model systems. However, aneuploidy is commonly found in cancer cells and often correlates with aggressive growth, suggesting that the impact of aneuploidy on cellular fitness is context dependent. The BRG1 (SMARCA4) subunit of the SWI/SNF chromatin remodelling complex is frequently lost in cancer. Here, we use a chromosomally stable cell line to test the effect of BRG1 loss on the evolution of aneuploidy. BRG1 deletion leads to an initial loss of fitness in this cell line that improves over time. Notably, we find increased tolerance to aneuploidy immediately upon loss of BRG1, and the fitness recovery over time correlates with chromosome gain. These data show that BRG1 loss creates an environment where karyotype changes can be explored without a fitness penalty. At least in some genetic backgrounds, therefore, BRG1 loss can affect the progression of tumourigenesis through tolerance of aneuploidy.

Suggested Citation

  • Federica Schiavoni & Pedro Zuazua-Villar & Theodoros I. Roumeliotis & Graeme Benstead-Hume & Mercedes Pardo & Frances M. G. Pearl & Jyoti S. Choudhary & Jessica A. Downs, 2022. "Aneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29420-3
    DOI: 10.1038/s41467-022-29420-3
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    1. Shelly Kalaora & Joo Sang Lee & Eilon Barnea & Ronen Levy & Polina Greenberg & Michal Alon & Gal Yagel & Gitit Bar Eli & Roni Oren & Aviyah Peri & Sushant Patkar & Lital Bitton & Steven A. Rosenberg &, 2020. "Immunoproteasome expression is associated with better prognosis and response to checkpoint therapies in melanoma," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
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