| Literature DB >> 31748743 |
Sihan Wu1, Kristen M Turner1,2, Nam Nguyen3,2, Ramya Raviram1, Marcella Erb4, Jennifer Santini4, Jens Luebeck5, Utkrisht Rajkumar3, Yarui Diao1,6,7, Bin Li1, Wenjing Zhang1, Nathan Jameson1, M Ryan Corces8, Jeffrey M Granja8, Xingqi Chen8,9, Ceyda Coruh10, Armen Abnousi11, Jack Houston1, Zhen Ye1, Rong Hu1, Miao Yu1, Hoon Kim12, Julie A Law10, Roel G W Verhaak12, Ming Hu11, Frank B Furnari1, Howard Y Chang13,14, Bing Ren15,16,17, Vineet Bafna18, Paul S Mischel19,20,21.
Abstract
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.Entities:
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Year: 2019 PMID： 31748743 PMCID： PMC7094777 DOI： 10.1038/s41586-019-1763-5
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 69.504