High resolution clonal architecture of hypomutated Wilms tumours

High resolution clonal architecture of hypomutated Wilms tumours

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 resoluti...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59854-4
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Summary: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.
ISSN:2041-1723

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