Molecular co-dependency of ecDNA in cancer
Oncogenes are frequently amplified on ecDNA, promoting massive oncogene expression due to the high copy number of ecDNAs and their unusually accessible chromatin. Therefore, cancer cells must evolve a set of mechanisms to maintain the ecDNA population and ensure its genetic function, creating ecDNA co-dependencies in cancer. These co-dependent mechanisms include ecDNA replication, transcription, epigenetic modification, and repair. However, our understanding of how cancer weaves these co-dependencies is still limited.
To uncover this mystery, we use whole-genome sequencing, epigenetic profiling, 3D genome capturing, and computational pipelines to characterize the ecDNA amplicon architecture, as well as its genetic and epigenetic features. We aim to extract this series of information to understand how ecDNA replicates, transcribes, and repairs, as well as how ecDNA’s unique accessibly chromatin and 3D topology impact these processes. We also use high-resolution imaging and protein mass spectrometry to characterize the core components responsible for ecDNA maintenance. We hope to leverage this knowledge to develop novel strategies to specifically target ecDNA in cancer and improve the current therapeutic regime.