Journal article

The site of breast cancer metastases dictates their clonal composition and reversible transcriptomic profile

Jean Berthelet, Verena C Wimmer, Holly J Whitfield, Antonin Serrano, Thomas Boudier, Stefano Mangiola, Michal Merdas, Farrah El-Saafin, David Baloyan, Jordan Wilcox, Steven Wilcox, Adam C Parslow, Anthony T Papenfuss, Belinda Yeo, Matthias Ernst, Bhupinder Pal, Robin L Anderson, Melissa J Davis, Kelly L Rogers, Frederic Hollande Show all

SCIENCE ADVANCES | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2021

Abstract

Intratumoral heterogeneity is a driver of breast cancer progression, but the nature of the clonal interactive network involved in this process remains unclear. Here, we optimized the use of optical barcoding to visualize and characterize 31 cancer subclones in vivo. By mapping the clonal composition of thousands of metastases in two clinically relevant sites, the lungs and liver, we found that metastases were highly polyclonal in lungs but not in the liver. Furthermore, the transcriptome of the subclones varied according to their metastatic niche. We also identified a reversible niche-driven signature that was conserved in lung and liver metastases collected during patient autopsies. Among t..

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Grants

Awarded by NBCF


Awarded by Susan G. Komen and Cancer Australia


Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

D.M., F.H., and B.P. are supported by the NBCF (Investigator Initiated Research Grant IIRS-19-082). D.M. is supported by Susan G. Komen and Cancer Australia (CCR19606878). F.H. is supported by the National Health and Medical Research Council of Australia (grant no. 1164081) and by a Senior Research Grant from the Tour de Cure Foundation. D.M., M.J.D., and B.Y. are supported by the Grant-in-Aid Scheme administered by Cancer Council Victoria. D.M., B.Y., and R.L.A. are supported by the Love Your Sister Foundation. R.L.A. and M.J.D. also acknowledge fellowship support from NBCF. The contents of the published material are solely the responsibility of the individual authors and do not reflect the views of Cancer Australia or other funding agencies.