Oncogenes are commonly amplified on particles of extrachromosomal DNA (ecDNA) in cancer1,2, but our understanding of the structure of ecDNA and its effect on gene regulation is limited. Here, by integrating ultrastructural imaging, long-range optical mapping and computational analysis of whole-genome sequencing, we demonstrate the structure of circular ecDNA. Pan-cancer analyses reveal that oncogenes encoded on ecDNA are among the most highly expressed genes in the transcriptome of the tumours, linking increased copy number with high transcription levels. Quantitative assessment of the chromatin state reveals that although ecDNA is packaged into chromatin with intact domain structure, it lacks higher-order compaction that is typical of chromosomes and displays significantly enhanced chromatin accessibility. Furthermore, ecDNA is shown to have a significantly greater number of ultra-long-range interactions with active chromatin, which provides insight into how the structure of circular ecDNA affects oncogene function, and connects ecDNA biology with modern cancer genomics and epigenetics.

Nature. 2019 Nov 20.

https://doi.org/10.1038/s41586-019-1763-5

同一实验室对ecDNA的早期研究分别发表于Science和Nature：

1. Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity.

Nature. 2017 Mar 2;543(7643):122-125. doi: 10.1038/nature21356. Epub 2017 Feb 8.

2.Targeted therapy resistance mediated by dynamic regulation of extrachromosomalmutant EGFRDNA.

Science. 2014 Jan 3;343(6166):72-6. doi: 10.1126/science.1241328. Epub 2013 Dec 5.