Speaker
Description
We explore the evolutionary dynamics of extrachromosomal DNA (ecDNA) in non-growing cell populations in the precancerous state. Unlike chromosomal DNA, ecDNA segregates randomly during mitosis, producing high variability in copy number across cells. While ecDNA has been studied in expanding tumours, its fate in precancerous populations is less understood. Stochastic simulations indicate that ecDNA dynamics differ markedly between weak and strong selection. Under weak selection, extinction of ecDNA+ cells is the most likely outcome. Conditional on survival, trajectories evolve slowly at low ecDNA+ frequency, allowing prolonged stochastic amplification to generate large copy number variability and, in rare cases, descendant cells that carry exceptionally high copy numbers. Under strong selection, rapid growth shortens this window and limits ecDNA amplification. These results identify conditions under which ecDNA-rich cells can arise in precancer and potentially seed malignant growth.
