[POS] Cancer Biology

[POS-22] Computational Analysis of Cancer Cell Dynamics with Extrachromosomal Circular DNA

*ZHILIN LIANG¹, Hiroshi Haeno¹ (1. Tokyo University of Science (Japan))

Keywords:

Extrachromosomal circular DNA,Mathematical modeling,Copy number amplification,Selective advantage

Extrachromosomal circular DNA (ecDNA) is circular DNA located outside chromosomes that contains oncogenes and enhancers. ecDNA is frequently observed in various cancer types, and its copy number shows significant variability among individual cells. The intratumoral heterogeneity of ecDNA suggests that it possesses specific mechanisms of replication and inheritance. However, the exact mechanisms by which ecDNA affects cellular behavior and how it is distributed during cell division remain unclear. This study focuses on two key aspects: copy number amplification and intratumoral heterogeneity. During cell division, chromosomal DNA in the nucleus replicates once and is then evenly distributed to daughter cells through mitosis, ensuring equal chromosomal copy numbers in each daughter cell. In contrast, ecDNA is unevenly distributed between daughter cells, leading to a binomial distribution pattern. By modeling this process, we successfully simulated tumorigenesis involving both ecDNA-positive and ecDNA-negative cells. Notably, we innovatively incorporated the parameter of cell death into the model, making the mathematical representation more realistic. The results demonstrate that when ecDNA provides a selective advantage to cells, ecDNA-positive cells become dominant during tumor progression. This study provides theoretical support for understanding the mechanisms of ecDNA-driven cancer evolution, as well as ecDNA-driven drug-resistance.