High resolution clonal architecture of hypomutated Wilms tumours
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.
Authors
- Sepide Derakhshan
- Yvonne Tiersma
- Maureen J. O’Sullivan (ORCID: https://orcid.org/0000-0001-5838-1609)
- Guillaume Morcrette
- Kathy Pritchard‐Jones (ORCID: https://orcid.org/0000-0002-2384-9475)
- Marry M. van den Heuvel‐Eibrink (ORCID: https://orcid.org/0000-0002-7760-879X)
- Henry Lee-Six (ORCID: https://orcid.org/0000-0003-4831-8088)
- Reem Al‐Saadi (ORCID: https://orcid.org/0000-0002-0816-5649)
- Jarno Drost (ORCID: https://orcid.org/0000-0002-2941-6179)
- Jenny Wegert (ORCID: https://orcid.org/0009-0009-4505-5519)
- J. Ciaran Hutchinson (ORCID: https://orcid.org/0000-0002-1708-2634)
- Tanzina Chowdhury (ORCID: https://orcid.org/0000-0003-3891-5778)
- Manàs Dave (ORCID: https://orcid.org/0000-0002-1676-801X)
- Michael R. Stratton (ORCID: https://orcid.org/0000-0001-6035-153X)
- Tim Coorens (ORCID: https://orcid.org/0000-0002-5826-3554)
- Ronald R. de Krijger (ORCID: https://orcid.org/0000-0001-6871-1296)
- Anna Wenger (ORCID: https://orcid.org/0000-0001-6063-5401)
- Sam Behjati (ORCID: https://orcid.org/0000-0002-6600-7665)
- Gordan Vujanić (ORCID: https://orcid.org/0000-0003-0726-6939)
- Yichen Wang (ORCID: https://orcid.org/0000-0001-5122-7545)
- Taryn D. Treger (ORCID: https://orcid.org/0000-0002-7204-4737)
- Manfred Gessler (ORCID: https://orcid.org/0000-0002-7915-6045)
- Nathaniel D. Anderson (ORCID: https://orcid.org/0000-0003-4523-6327)
- Sanne de Haan
- Conor Parks (ORCID: https://orcid.org/0000-0003-0240-0684)
- Aleksandra Letunovska
- Alice Lawford
Institutions
- Broad Institute (US)
- Trinity College Dublin (IE)
- University of Cambridge (GB)
- Great Ormond Street Hospital (GB)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Wellcome Sanger Institute (GB)
- University of Manchester (GB)
- Children's Health Ireland at Crumlin (IE)
- University Medical Center Utrecht (NL)
- Comprehensive Cancer Center Mainfranken (DE)
- Oncode Institute (NL)
- Princess Máxima Center (NL)
- University College London (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-29
- DOI
- https://doi.org/10.1038/s41467-025-59854-4
- Citations
- 3
- Primary Topic
- Renal and related cancers
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- Wellcome
- Wellcome Trust
- Children's Cancer and Leukaemia Group
- Wenner-Gren Stiftelserna
- Cancer Research UK
- National Institute for Health and Care Research
- University College London
- Little Princess Trust
- Trinity College, University of Cambridge