IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-21675-6.html
   My bibliography  Save this article

Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours

Author

Listed:
  • Lars Custers

    (Princess Máxima Center for Pediatric Oncology
    Oncode Institute)

  • Eleonora Khabirova

    (Wellcome Sanger Institute)

  • Tim H. H. Coorens

    (Wellcome Sanger Institute)

  • Thomas R. W. Oliver

    (Wellcome Sanger Institute
    Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Camilla Calandrini

    (Princess Máxima Center for Pediatric Oncology
    Oncode Institute)

  • Matthew D. Young

    (Wellcome Sanger Institute)

  • Felipe A. Vieira Braga

    (University of Amsterdam)

  • Peter Ellis

    (Wellcome Sanger Institute)

  • Lira Mamanova

    (Wellcome Sanger Institute)

  • Heidi Segers

    (University Hospital Leuven)

  • Arie Maat

    (Princess Máxima Center for Pediatric Oncology)

  • Marcel Kool

    (Princess Máxima Center for Pediatric Oncology
    Hopp Children’s Cancer Center (KiTZ)
    German Cancer Research Center DKFZ and German Cancer Consortium DKTK)

  • Eelco W. Hoving

    (Princess Máxima Center for Pediatric Oncology)

  • Marry M. Heuvel-Eibrink

    (Princess Máxima Center for Pediatric Oncology)

  • James Nicholson

    (Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Karin Straathof

    (UCL Great Ormond Street Hospital Institute of Child Health Biomedical Research Centre
    Great Ormond Street Hospital for Children NHS Foundation Trust)

  • Liz Hook

    (Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Ronald R. Krijger

    (Princess Máxima Center for Pediatric Oncology
    University Medical Center Utrecht)

  • Claire Trayers

    (Cambridge University Hospitals NHS Foundation Trust)

  • Kieren Allinson

    (Cambridge University Hospitals NHS Foundation Trust)

  • Sam Behjati

    (Wellcome Sanger Institute
    Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Jarno Drost

    (Princess Máxima Center for Pediatric Oncology
    Oncode Institute)

Abstract

Malignant rhabdoid tumour (MRT) is an often lethal childhood cancer that, like many paediatric tumours, is thought to arise from aberrant fetal development. The embryonic root and differentiation pathways underpinning MRT are not firmly established. Here, we study the origin of MRT by combining phylogenetic analyses and single-cell mRNA studies in patient-derived organoids. Comparison of somatic mutations shared between cancer and surrounding normal tissues places MRT in a lineage with neural crest-derived Schwann cells. Single-cell mRNA readouts of MRT differentiation, which we examine by reverting the genetic driver mutation underpinning MRT, SMARCB1 loss, suggest that cells are blocked en route to differentiating into mesenchyme. Quantitative transcriptional predictions indicate that combined HDAC and mTOR inhibition mimic MRT differentiation, which we confirm experimentally. Our study defines the developmental block of MRT and reveals potential differentiation therapies.

Suggested Citation

  • Lars Custers & Eleonora Khabirova & Tim H. H. Coorens & Thomas R. W. Oliver & Camilla Calandrini & Matthew D. Young & Felipe A. Vieira Braga & Peter Ellis & Lira Mamanova & Heidi Segers & Arie Maat & , 2021. "Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21675-6
    DOI: 10.1038/s41467-021-21675-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-21675-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-21675-6?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. Jeff DeMartino & Michael T. Meister & Lindy L. Visser & Mariël Brok & Marian J. A. Groot Koerkamp & Amber K. L. Wezenaar & Laura S. Hiemcke-Jiwa & Terezinha Souza & Johannes H. M. Merks & Anne C. Rios, 2023. "Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Ning Qing Liu & Irene Paassen & Lars Custers & Peter Zeller & Hans Teunissen & Dilara Ayyildiz & Jiayou He & Juliane Laura Buhl & Eelco Wieger Hoving & Alexander Oudenaarden & Elzo Wit & Jarno Drost, 2023. "SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Monika Graf & Marta Interlandi & Natalia Moreno & Dörthe Holdhof & Carolin Göbel & Viktoria Melcher & Julius Mertins & Thomas K. Albert & Dennis Kastrati & Amelie Alfert & Till Holsten & Flavia de Far, 2022. "Single-cell transcriptomics identifies potential cells of origin of MYC rhabdoid tumors," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. María-Jesús Lobón-Iglesias & Mamy Andrianteranagna & Zhi-Yan Han & Céline Chauvin & Julien Masliah-Planchon & Valeria Manriquez & Arnault Tauziede-Espariat & Sandrina Turczynski & Rachida Bouarich-Bou, 2023. "Imaging and multi-omics datasets converge to define different neural progenitor origins for ATRT-SHH subgroups," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    5. Bujamin H. Vokshi & Guillaume Davidson & Nassim Tawanaie Pour Sedehi & Alexandra Helleux & Marc Rippinger & Alexandre R. Haller & Justine Gantzer & Jonathan Thouvenin & Philippe Baltzinger & Rachida B, 2023. "SMARCB1 regulates a TFCP2L1-MYC transcriptional switch promoting renal medullary carcinoma transformation and ferroptosis resistance," Nature Communications, Nature, vol. 14(1), pages 1-19, 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:12:y:2021:i:1:d:10.1038_s41467-021-21675-6. 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.