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Intratumor heterogeneity reflects clinical disease course

Intratumoral genetic heterogeneity of driver somatic mutations is present in a variety of tumor types, yet the extent of heterogeneity is variable. We propose that this variation is a reflection of the inherent biology of a given tumor type, representing the pace of metastatic dissemination and hence clinical disease course.

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Fig. 1: Evolutionary trajectories in solid tumors and relationship to clinical course.

References

  1. Greaves, M. Cancer Discov. 5, 806–820 (2015).

    Article  CAS  Google Scholar 

  2. Greaves, M. Nat. Rev. Cancer 7, 213–221 (2007).

    Article  CAS  Google Scholar 

  3. Gillies, R. J., Verduzco, D. & Gatenby, R. A. Nat. Rev. Cancer 12, 487–493 (2012).

    Article  CAS  Google Scholar 

  4. Williams, M. J. et al. Nat. Genet. 50, 895–903 (2018).

    Article  CAS  Google Scholar 

  5. Greaves, M. & Maley, C. C. Nature 481, 306–313 (2012).

    Article  CAS  Google Scholar 

  6. Turajlic, S. et al. Cell 173, 595–610 (2018).

    Article  CAS  Google Scholar 

  7. Makohon-Moore, A. P. et al. Nat. Genet. 49, 358–366 (2017).

    Article  CAS  Google Scholar 

  8. Maley, C. C. et al. Nat. Rev. Cancer 17, 605–619 (2017).

    Article  CAS  Google Scholar 

  9. Krabbe, L.-M., Bagrodia, A., Margulis, V. & Wood, C. Semin. Intervent. Radiol. 31, 27–32 (2014).

    Article  Google Scholar 

  10. Kleeff, J. et al. Nat. Rev. Dis. Primers 2, 16022 (2016).

    Article  Google Scholar 

  11. Winter, J. M. et al. Ann. Surg. Oncol. 19, 169–175 (2012).

    Article  Google Scholar 

  12. Turajlic, S. et al. Cell 173, 581–594 (2018).

    Article  CAS  Google Scholar 

  13. McDonald, O. G. O. G. et al. Nat. Genet. 49, 367–376 (2017).

    Article  CAS  Google Scholar 

  14. Gomez, K. et al. BMC Cancer 18, 85 (2018).

    Article  Google Scholar 

  15. Gundem, G. et al. Nature 520, 353–357 (2015).

    Article  CAS  Google Scholar 

  16. Kohutek, Z. A. et al. Cold Spring Harb. Mol. Case Stud. 3, a001701 (2017).

    Article  Google Scholar 

  17. Blakely, C. M. et al. Nat. Genet. 49, 1693–1704 (2017).

    Article  CAS  Google Scholar 

  18. Juric, D. et al. Nature 518, 240–244 (2015).

    Article  CAS  Google Scholar 

  19. Jamal-Hanjani, M. et al. N. Engl. J. Med. 376, 2109–2121 (2017).

    Article  CAS  Google Scholar 

  20. Kovac, M. et al. Nat. Commun. 6, 6336 (2015).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Research support by CA179991 and CA220508 to C.A.I.D., who also receives research support from Bristol-Myers Squibb. K.L. is supported by a UK Medical Research Council Skills Development Fellowship Award (grant reference number MR/P014712/1). C.S. is supported by the Francis Crick Institute that receives its core funding from Cancer Research UK (FC001169,FC001202), the UK Medical Research Council (FC001169, FC001202), and the Wellcome Trust (FC001169, FC001202) and from Cancer Research UK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), the CRUK Lung Cancer Centre of Excellence, Stand Up 2 Cancer (SU2C), the Rosetrees Trust, NovoNordisk Foundation (ID16584) and the Breast Cancer Research Foundation (BCRF), European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ ERC grant agreement n°FP7 – 617844 (PROTEUS) and Marie Curie Network PloidyNet.

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Correspondence to Christine A. Iacobuzio-Donahue or Charles Swanton.

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Iacobuzio-Donahue, C.A., Litchfield, K. & Swanton, C. Intratumor heterogeneity reflects clinical disease course. Nat Cancer 1, 3–6 (2020). https://doi.org/10.1038/s43018-019-0002-1

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