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  • Wu, SihanUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA (author)

Circular ecDNA promotes accessible chromatin and high oncogene expression

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-11-20
  • NATURE PUBLISHING GROUP,2019
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-400684
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-400684URI
  • https://doi.org/10.1038/s41586-019-1763-5DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Turner, Kristen M.Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA;Boundless Bio Inc, La Jolla, CA USA (author)
  • Nguyen, Nam (author)
  • Raviram, RamyaUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA (author)
  • Erb, MarcellaUniv Calif San Diego, Dept Neurosci, UCSD Light Microscopy Core Facil, La Jolla, CA 92093 USA (author)
  • Santini, JenniferUniv Calif San Diego, Dept Neurosci, UCSD Light Microscopy Core Facil, La Jolla, CA 92093 USA (author)
  • Luebeck, JensUniv Calif San Diego, Bioinformat & Syst Biol Grad Program, La Jolla, CA 92093 USA (author)
  • Rajkumar, UtkrishtUniv Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA;Duke Univ, Sch Med, Dept Cell Biol, Regenerat Next Initiat, Durham, NC USA (author)
  • Diao, YaruiUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA;Duke Univ, Sch Med, Dept Orthopaed Surg, Regenerat Next Initiat, Durham, NC USA (author)
  • Li, BinUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA (author)
  • Zhang, WenjingUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA (author)
  • Jameson, NathanUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA (author)
  • Corces, M. RyanStanford Univ, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA (author)
  • Granja, Jeffrey M.Stanford Univ, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA (author)
  • Chen, XingqiUppsala universitet,Molekylära verktyg,Stanford Univ, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA(Swepub:uu)xinch196 (author)
  • Coruh, CeydaSalk Inst Biol Studies, Plant Mol & Cellular Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA (author)
  • Abnousi, ArmenCleveland Clin Fdn, Lerner Res Inst, Dept Quantitat Hlth Sci, 9500 Euclid Ave, Cleveland, OH 44195 USA (author)
  • Houston, JackUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA (author)
  • Ye, ZhenUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA (author)
  • Hu, RongUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA (author)
  • Yu, MiaoUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA (author)
  • Kim, HoonJackson Lab Genom Med, Farmington, CT USA (author)
  • Law, Julie A.Salk Inst Biol Studies, Plant Mol & Cellular Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA (author)
  • Verhaak, Roel G. W.Jackson Lab Genom Med, Farmington, CT USA (author)
  • Hu, MingCleveland Clin Fdn, Lerner Res Inst, Dept Quantitat Hlth Sci, 9500 Euclid Ave, Cleveland, OH 44195 USA (author)
  • Furnari, Frank B.Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA (author)
  • Chang, Howard Y.Stanford Univ, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA;Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA (author)
  • Ren, BingUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA;Univ Calif San Diego, Ctr Epigen, Dept Cellular & Mol Med, La Jolla, CA 92093 USA;Univ Calif San Diego, Moores Canc Ctr, Inst Genom Med, La Jolla, CA 92093 USA (author)
  • Bafna, VineetUniv Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA (author)
  • Mischel, Paul S.Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA;Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA;Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA (author)
  • Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USAUniv Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA;Boundless Bio Inc, La Jolla, CA USA (creator_code:org_t)

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  • In:Nature: NATURE PUBLISHING GROUP575:7784, s. 699-7030028-08361476-4687

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