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CANCER BIOLOGY

Targeting BRCA-mutated tumors in mitosis

Nature Cancer volume 2, pages 1296–1297 (2021)Cite this article

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A genome-wide CRISPR screen finds CIP2A as a new synthetic lethal target for BRCA1- and BRCA2-deficient cells. Unlike PARP inhibition that increases replication-induced DNA double-strand breaks and radial chromosomes, depleting CIP2A or disrupting its interaction with TOPBP1 increases micronuclei and chromosomal missegregation, revealing a mitotic target for BRCA-mutated tumors.

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Fig. 1: BRCA1- and BRCA2-deficient cells accumulate DNA damage and breaks in mitosis probably caused by incomplete chromosome replication, particularly in the absence of TP53.

References

  1. Farmer, H. et al. Nature 434, 917–921 (2005).

    Article  CAS  Google Scholar 

  2. Bryant, H. E. et al. Nature 434, 913–917 (2005).

    Article  CAS  Google Scholar 

  3. Lord, C. J. & Ashworth, A. Nat. Med. 19, 1381–1388 (2013).

    Article  CAS  Google Scholar 

  4. Adam, S. et al. Nat. Cancer https://doi.org/10.1038/s43018-021-00266-w (2021).

  5. Mengwasser, K. E. et al. Mol. Cell 73, 885–899 (2019).

    Article  CAS  Google Scholar 

  6. Alvarez-Quilon, A. et al. Mol. Cell 78, 1152–1165 (2020).

    Article  CAS  Google Scholar 

  7. Soofiyani, S. R., Hejazi, M. S. & Baradaran, B. Biomed. Pharmacother. 96, 626–633 (2017).

    Article  CAS  Google Scholar 

  8. Come, C. et al. Clin. Cancer Res. 15, 5092–5100 (2009).

    Article  CAS  Google Scholar 

  9. Junttila, M. R. et al. Cell 130, 51–62 (2007).

    Article  CAS  Google Scholar 

  10. Ventela, S. et al. PLoS ONE 7, e33209 (2012).

    Article  CAS  Google Scholar 

  11. Laine, A. et al. Cancer Res. 81, 4319–4331 (2021).

    Article  CAS  Google Scholar 

  12. Leimbacher, P. A. et al. Mol. Cell 74, 571–583 (2019).

    Article  CAS  Google Scholar 

  13. De Marco Zompit, M. et al. Preprint at bioRxiv https://doi.org/10.1101/2021.02.08.430274 (2021).

  14. Hustedt, N. et al. Open Biol. 9, 190156 (2019).

    Article  CAS  Google Scholar 

  15. Sidi, S. et al. Cell 133, 864–877 (2008).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

D.M. was a senior fellow of the Leukemia & Lymphoma Society. The work is in part supported by NIH1R01CA215067 to S.Z.

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Authors and Affiliations

  1. Institute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Demis Menolfi & Shan Zha

  2. Division of Pediatric Oncology, Hematology and Stem Cell Transplantation, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Shan Zha

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  1. Demis Menolfi
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  2. Shan Zha
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Correspondence to Shan Zha.

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Menolfi, D., Zha, S. Targeting BRCA-mutated tumors in mitosis. Nat Cancer 2, 1296–1297 (2021). https://doi.org/10.1038/s43018-021-00293-7

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