Single-cell phylodynamics reveal rapid late-stage colorectal cancer expansions

João M. Alves; Kylie Chen; Sonia Prado‐Lòpez; Nuria Estévez‐Gómez; Pilar Alvariño; Juana Alonso; Monica Vishnu Valecha; Laura Tomás; Antoine Zwaans; Ugnė Stolz; Tanja Stadler; Débora Chantada; José Cameselle‐Teijeiro; Alexei J. Drummond; David Posada

doi:10.1101/2025.11.25.690378

Evolutionary BiologybioRxivNov 25, 2025

Preprint

Single-cell phylodynamics reveal rapid late-stage colorectal cancer expansions

João M. Alves iD, Kylie Chen iD, Sonia Prado‐Lòpez iD, Nuria Estévez‐Gómez iD, Pilar Alvariño iD, Juana Alonso, Monica Vishnu Valecha iD, Laura Tomás iD, Antoine Zwaans iD, Ugnė Stolz iD, Tanja Stadler iD, Débora Chantada iD, José Cameselle‐Teijeiro iD, Alexei J. Drummond iD, David Posada iD

Abstract

Single-cell whole-genome sequencing of 335 cells from seven colorectal cancers, coupled with Bayesian phylodynamic modeling, revealed tumors often originate decades before diagnosis, remain indolent, and expand rapidly within two years. Strong spatial structuring with minimal interregional mixing was observed, while substitution rates varied widely and were decoupled from growth. Our findings highlight extended evolutionary stasis and sudden expansion, informing strategies for early detection and intervention.

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