Nature Communications (May 2025)
High resolution clonal architecture of hypomutated Wilms tumours
- Henry Lee-Six,
- Taryn D. Treger,
- Manas Dave,
- Tim HH Coorens,
- Nathaniel D. Anderson,
- Yvonne Tiersma,
- Sepide Derakhshan,
- Sanne de Haan,
- Marry M. van den Heuvel-Eibrink,
- Yichen Wang,
- Anna Wenger,
- Reem Al-Saadi,
- Alice Lawford,
- Aleksandra Letunovska,
- Jenny Wegert,
- Conor Parks,
- Guillaume Morcrette,
- Manfred Gessler,
- Gordan Vujanic,
- Tanzina Chowdhury,
- Maureen J O’Sullivan,
- Ronald R. de Krijger,
- Michael R. Stratton,
- Kathy Pritchard-Jones,
- J. Ciaran Hutchinson,
- Jarno Drost,
- Sam Behjati
Affiliations
- Henry Lee-Six
- Wellcome Sanger Institute
- Taryn D. Treger
- Wellcome Sanger Institute
- Manas Dave
- Wellcome Sanger Institute
- Tim HH Coorens
- Broad Institute of MIT and Harvard
- Nathaniel D. Anderson
- Wellcome Sanger Institute
- Yvonne Tiersma
- Princess Máxima Center for Pediatric Oncology
- Sepide Derakhshan
- Princess Máxima Center for Pediatric Oncology
- Sanne de Haan
- Princess Máxima Center for Pediatric Oncology
- Marry M. van den 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
- Alice Lawford
- Great Ormond Street Hospital for Children
- Aleksandra Letunovska
- UCL Great Ormond Street Institute of Child Health
- Jenny Wegert
- Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Würzburg University & Comprehensive Cancer Center Mainfranken
- Conor Parks
- Wellcome Sanger Institute
- Guillaume Morcrette
- UCL Great Ormond Street Institute of Child Health
- Manfred Gessler
- Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Würzburg University & Comprehensive Cancer Center Mainfranken
- Gordan Vujanic
- Department of Pathology, Sidra Medicine
- Tanzina Chowdhury
- UCL Great Ormond Street Institute of Child Health
- Maureen J O’Sullivan
- Department of Pathology, Children’s Health Ireland at Crumlin
- Ronald R. de Krijger
- Princess Máxima Center for Pediatric Oncology
- 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
- Sam Behjati
- Wellcome Sanger Institute
- DOI
- https://doi.org/10.1038/s41467-025-59854-4
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 10
Abstract
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.
