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Circular ecDNA promotes accessible chromatin and high oncogene expression
Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.ORCID iD: 0000-0001-8329-7492
Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA;Boundless Bio Inc, La Jolla, CA USA.
Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
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2019 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 575, no 7784, p. 699-703Article in journal (Refereed) Published
Abstract [en]

Oncogenes are commonly amplified on particles of extrachromosomal DNA (ecDNA) in cancer(1,2), 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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 575, no 7784, p. 699-703
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Genetics
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URN: urn:nbn:se:uu:diva-400684DOI: 10.1038/s41586-019-1763-5ISI: 000500036800066PubMedID: 31748743OAI: oai:DiVA.org:uu-400684DiVA, id: diva2:1382161
Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-01-02Bibliographically approved

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Chen, Xingqi

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