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High resolution clonal architecture of hypomutated Wilms tumours

Author

Listed:
  • Henry Lee-Six

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

  • Taryn D. Treger

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

  • Manas Dave

    (Wellcome Sanger Institute
    The University of Cambridge
    The University of Manchester)

  • Tim HH Coorens

    (Broad Institute of MIT and Harvard)

  • Nathaniel D. Anderson

    (Wellcome Sanger Institute)

  • Yvonne Tiersma

    (Princess Máxima Center for Pediatric Oncology
    Oncode Institute)

  • Sepide Derakhshan

    (Princess Máxima Center for Pediatric Oncology
    Oncode Institute)

  • Sanne Haan

    (Princess Máxima Center for Pediatric Oncology
    Oncode Institute)

  • Marry M. Heuvel-Eibrink

    (Princess Máxima Center for Pediatric Oncology)

  • Yichen Wang

    (Wellcome Sanger Institute)

  • Anna Wenger

    (Wellcome Sanger Institute)

  • Reem Al-Saadi

    (UCL Great Ormond Street Institute of Child Health
    Great Ormond Street Hospital for Children)

  • Alice Lawford

    (Great Ormond Street Hospital for Children)

  • Aleksandra Letunovska

    (UCL Great Ormond Street Institute of Child Health
    Great Ormond Street Hospital for Children)

  • Jenny Wegert

    (Würzburg University & Comprehensive Cancer Center Mainfranken)

  • Conor Parks

    (Wellcome Sanger Institute)

  • Guillaume Morcrette

    (UCL Great Ormond Street Institute of Child Health
    Great Ormond Street Hospital for Children)

  • Manfred Gessler

    (Würzburg University & Comprehensive Cancer Center Mainfranken)

  • Gordan Vujanic

    (Sidra Medicine)

  • Tanzina Chowdhury

    (UCL Great Ormond Street Institute of Child Health
    Great Ormond Street Hospital for Children)

  • Maureen J O’Sullivan

    (Children’s Health Ireland at Crumlin
    Trinity College)

  • Ronald R. Krijger

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

  • Michael R. Stratton

    (Wellcome Sanger Institute)

  • Kathy Pritchard-Jones

    (UCL Great Ormond Street Institute of Child Health)

  • J. Ciaran Hutchinson

    (Great Ormond Street Hospital for Children)

  • Jarno Drost

    (Princess Máxima Center for Pediatric Oncology
    Oncode Institute)

  • Sam Behjati

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

Abstract

A paradigm of childhood cancers is that they have a low mutation burden, with some ostensibly bearing fewer mutations than the normal tissues from which they derive. We set out to resolve this paradox by examining paediatric renal cancers with exceptionally few mutations using high resolution, high depth sequencing approaches. We find that apparent hypomutation is the result of unusual clonal architecture due to a normal tissue-like mode of tumour evolution, raising the possibility that the mutation burden of some cancers has been systematically misjudged.

Suggested Citation

  • Henry Lee-Six & Taryn D. Treger & Manas Dave & Tim HH Coorens & Nathaniel D. Anderson & Yvonne Tiersma & Sepide Derakhshan & Sanne Haan & Marry M. Heuvel-Eibrink & Yichen Wang & Anna Wenger & Reem Al-, 2025. "High resolution clonal architecture of hypomutated Wilms tumours," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59854-4
    DOI: 10.1038/s41467-025-59854-4
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