"Exploring the Role of Fitness Function of Extrachromosomal DNA (ecDNA) in Cancer Evolution"Tu, FengyuExtrachromosomal DNA (ecDNA), a circular DNA element, plays a crucial role in cancer development and heterogeneity. Its unique structure allows rapid and random segregation into daughter cells, leading to rapid changes in copy number. Tumor cells harboring ecDNA often exhibit heightened aggressiveness and enhanced fitness. However, the extent to which cellular fitness depends on ecDNA copy number remains poorly understood due to the scarcity of theoretical models addressing this relationship. In contrast to existing models neglecting copy number dependency, we propose utilizing a sigmoid equation as a fitness function to investigate the evolutionary dynamics of ecDNA in cancer cell populations experiencing positive selection. We employ stochastic simulations and propose theoretical experiments involving single-cell sampling to explore the dependency of cellular fitness on ecDNA copy number. Additionally, we utilize approximate Bayesian inference to estimate parameters of the fitness equation. The presence of the fitness equation leads to a bimodal distribution of ecDNA in cancer cell populations under specific parameters. Theoretical experiments using single-cell sampling reveal variations in tumor cell growth time and ecDNA distribution, which might provide theoretical support for its existence. Furthermore, parameter estimation employing the ABC algorithm suggests ideal inference for the initial number of ecDNAs and the fitness equation model. Our theoretical framework offers valuable insights into verifying copy number-dependent fitness equations and understanding the evolutionary dynamics of ecDNA. These findings hold promise for validation in real experiments, providing crucial insights into ecDNA evolution dynamics. |
« back