IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-19452-y.html
   My bibliography  Save this article

Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma

Author

Listed:
  • Konstantin Helmsauer

    (Charité—Universitätsmedizin Berlin)

  • Maria E. Valieva

    (Max Planck Institute for Molecular Genetics
    Charité—Universitätsmedizin Berlin)

  • Salaheddine Ali

    (Max Planck Institute for Molecular Genetics
    Charité—Universitätsmedizin Berlin
    Charité—Universitätsmedizin Berlin)

  • Rocío Chamorro González

    (Charité—Universitätsmedizin Berlin)

  • Robert Schöpflin

    (Max Planck Institute for Molecular Genetics
    Charité—Universitätsmedizin Berlin)

  • Claudia Röefzaad

    (Max Delbrück Center for Molecular Medicine and Charité—Universitätsmedizin Berlin)

  • Yi Bei

    (Charité—Universitätsmedizin Berlin)

  • Heathcliff Dorado Garcia

    (Charité—Universitätsmedizin Berlin)

  • Elias Rodriguez-Fos

    (Joint BSC-CRG-IRB Research Program in Computational Biology)

  • Montserrat Puiggròs

    (Joint BSC-CRG-IRB Research Program in Computational Biology)

  • Katharina Kasack

    (partner site Berlin, and German Cancer Research Center DKFZ)

  • Kerstin Haase

    (Charité—Universitätsmedizin Berlin)

  • Csilla Keskeny

    (Charité—Universitätsmedizin Berlin
    partner site Berlin, and German Cancer Research Center DKFZ)

  • Celine Y. Chen

    (Charité—Universitätsmedizin Berlin)

  • Luis P. Kuschel

    (Charité—Universitätsmedizin Berlin)

  • Philipp Euskirchen

    (partner site Berlin, and German Cancer Research Center DKFZ
    Charité—Universitätsmedizin Berlin
    Berlin Institute of Health)

  • Verena Heinrich

    (Max Planck Institute for Molecular Genetics)

  • Michael I. Robson

    (Max Planck Institute for Molecular Genetics)

  • Carolina Rosswog

    (University of Cologne)

  • Joern Toedling

    (Charité—Universitätsmedizin Berlin)

  • Annabell Szymansky

    (Charité—Universitätsmedizin Berlin)

  • Falk Hertwig

    (Charité—Universitätsmedizin Berlin)

  • Matthias Fischer

    (University of Cologne)

  • David Torrents

    (Joint BSC-CRG-IRB Research Program in Computational Biology
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

  • Angelika Eggert

    (Charité—Universitätsmedizin Berlin
    partner site Berlin, and German Cancer Research Center DKFZ
    Berlin Institute of Health)

  • Johannes H. Schulte

    (Charité—Universitätsmedizin Berlin
    partner site Berlin, and German Cancer Research Center DKFZ
    Berlin Institute of Health)

  • Stefan Mundlos

    (Max Planck Institute for Molecular Genetics
    Charité—Universitätsmedizin Berlin
    Charité—Universitätsmedizin Berlin)

  • Anton G. Henssen

    (Charité—Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine and Charité—Universitätsmedizin Berlin
    partner site Berlin, and German Cancer Research Center DKFZ
    Berlin Institute of Health)

  • Richard P. Koche

    (Berlin Institute of Health
    Memorial Sloan Kettering Cancer Center)

Abstract

MYCN amplification drives one in six cases of neuroblastoma. The supernumerary gene copies are commonly found on highly rearranged, extrachromosomal circular DNA (ecDNA). The exact amplicon structure has not been described thus far and the functional relevance of its rearrangements is unknown. Here, we analyze the MYCN amplicon structure using short-read and Nanopore sequencing and its chromatin landscape using ChIP-seq, ATAC-seq and Hi-C. This reveals two distinct classes of amplicons which explain the regulatory requirements for MYCN overexpression. The first class always co-amplifies a proximal enhancer driven by the noradrenergic core regulatory circuit (CRC). The second class of MYCN amplicons is characterized by high structural complexity, lacks key local enhancers, and instead contains distal chromosomal fragments harboring CRC-driven enhancers. Thus, ectopic enhancer hijacking can compensate for the loss of local gene regulatory elements and explains a large component of the structural diversity observed in MYCN amplification.

Suggested Citation

  • Konstantin Helmsauer & Maria E. Valieva & Salaheddine Ali & Rocío Chamorro González & Robert Schöpflin & Claudia Röefzaad & Yi Bei & Heathcliff Dorado Garcia & Elias Rodriguez-Fos & Montserrat Puiggrò, 2020. "Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19452-y
    DOI: 10.1038/s41467-020-19452-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-19452-y
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-020-19452-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Jinxin Phaedo Chen & Constantin Diekmann & Honggui Wu & Chong Chen & Giulia Chiara & Enrico Berrino & Konstantinos L. Georgiadis & Britta A. M. Bouwman & Mohit Virdi & Luuk Harbers & Sara Erika Bellom, 2024. "scCircle-seq unveils the diversity and complexity of extrachromosomal circular DNAs in single cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Karin Schmelz & Joern Toedling & Matt Huska & Maja C. Cwikla & Louisa-Marie Kruetzfeldt & Jutta Proba & Peter F. Ambros & Inge M. Ambros & Sengül Boral & Marco Lodrini & Celine Y. Chen & Martin Burker, 2021. "Spatial and temporal intratumour heterogeneity has potential consequences for single biopsy-based neuroblastoma treatment decisions," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Mark W. Youngblood & Zeynep Erson-Omay & Chang Li & Hinda Najem & Süleyman Coșkun & Evgeniya Tyrtova & Julio D. Montejo & Danielle F. Miyagishima & Tanyeri Barak & Sayoko Nishimura & Akdes Serin Harma, 2023. "Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Alexandra D’Oto & Jie Fang & Hongjian Jin & Beisi Xu & Shivendra Singh & Anoushka Mullasseril & Victoria Jones & Ahmed Abu-Zaid & Xinyu Buttlar & Bailey Cooke & Dongli Hu & Jason Shohet & Andrew J. Mu, 2021. "KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    5. Yanli Liu & Zhong Wu & Jin Zhou & Dinesh K. A. Ramadurai & Katelyn L. Mortenson & Estrella Aguilera-Jimenez & Yifei Yan & Xiaojun Yang & Alison M. Taylor & Katherine E. Varley & Jason Gertz & Peter S., 2021. "A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    6. Katelyn L. Mortenson & Courtney Dawes & Emily R. Wilson & Nathan E. Patchen & Hailey E. Johnson & Jason Gertz & Swneke D. Bailey & Yang Liu & Katherine E. Varley & Xiaoyang Zhang, 2024. "3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19452-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.