Molecular functions of ecDNA in cancer
DNA encodes information both in its sequence and its shape. To date, we have obtained clear images of ecDNA, showing its circular configuration and acentric nature. These two features allow ecDNA to increase its copy number rapidly, generating more and more templates for oncogene expression. Furthermore, the random segregation of ecDNA during mitosis boosts the cancer heterogeneity dramatically, freeing cancer from the constrain of Mendelian inheritance to evolve and adapt to the ever-changing microenvironment quickly.
Nonetheless, we still lack the knowledge of how ecDNA impacts the cancer genome, such as transcriptional activity. As a piece of genetic material, ecDNA also serves as a template for gene transcription. However, its small size, high copy number, hyper-accessible chromatin, and spatial localization allow it to freely interact with the cancer genome, including ecDNA–ecDNA and ecDNA–chromosomal DNA interactions. We are interested in characterizing these interactions by integrating modern sequencing and high-resolution imaging approaches to understanding how the unique physical feature and spatial organization of ecDNA act on cancer transcriptome and cellular behaviors.