Punctuational evolution is pervasive in distal site metastatic colonization

Butler, G. ORCID: https://orcid.org/0000-0002-6207-6225, Amend, S. R., Venditti, C. ORCID: https://orcid.org/0000-0002-6776-2355 and Pienta, K. J. (2025) Punctuational evolution is pervasive in distal site metastatic colonization. Proceedings of the Royal Society B: Biological Sciences, 292 (2039). ISSN 1471-2954 doi: 10.1098/rspb.2024.2850

Abstract/Summary

The evolution of metastasis, the spread of cancer to distal sites within the body, represents a lethal stage of cancer progression. Yet, the evolutionary dynamics that shape the emergence of metastatic disease remain unresolved. Here, using single-cell lineage tracing data in combination with phylogenetic statistical methods, we show that the evolutionary trajectory of metastatic disease is littered with bursts of rapid molecular change as new cellular subpopulations appear, a pattern known as punctuational evolution. Next, by measuring punctuational evolution across the metastatic cascade, we show that punctuational effects are concentrated within the formation of secondary tumours at distal metastatic sites, suggesting that qualitatively different modes of evolution may drive primary and metastatic tumour progression. Taken as a whole, our findings provide empirical evidence for distinct patterns of molecular evolution at early and late stages of metastatic disease and our approach provides a framework to study the evolution of metastasis at a more nuanced level than has been previously possible.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/120538
Identification Number/DOI	10.1098/rspb.2024.2850
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Ecology and Evolutionary Biology
Publisher	The Royal Society
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