Nature Communications

High resolution clonal architecture of hypomutated Wilms tumours

H Henry Lee-Six T Taryn D. Treger M Manas Dave T Tim HH Coorens N Nathaniel D. Anderson Y Yvonne Tiersma (Division of Tumor Biology and Immunology, The Netherlands Cancer Institute) S Sepide Derakhshan S Sanne de Haan M Marry M. van den Heuvel-Eibrink Y Yichen Wang A Anna Wenger R Reem Al-Saadi A Alice Lawford A Aleksandra Letunovska J Jenny Wegert C Conor Parks G Guillaume Morcrette M Manfred Gessler G Gordan Vujanic T Tanzina Chowdhury M Maureen J O’Sullivan R Ronald R. de Krijger (Princess Máxima Center for Pediatric Oncology) M Michael R. Stratton K Kathy Pritchard-Jones J J. Ciaran Hutchinson J Jarno Drost S Sam Behjati

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.

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Article Details

Volume / Issue Vol. 16, Issue 1
Published May 29, 2025
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio
ISSN: 2041-1723 Open Access Life Sciences

Authors (27)

H

Henry Lee-Six

T

Taryn D. Treger

M

Manas Dave

T

Tim HH Coorens

N

Nathaniel D. Anderson

Y

Yvonne Tiersma

Division of Tumor Biology and Immunology, The Netherlands Cancer Institute

S

Sepide Derakhshan

S

Sanne de Haan

M

Marry M. van den Heuvel-Eibrink

Y

Yichen Wang

A

Anna Wenger

R

Reem Al-Saadi

A

Alice Lawford

A

Aleksandra Letunovska

J

Jenny Wegert

C

Conor Parks

G

Guillaume Morcrette

M

Manfred Gessler

G

Gordan Vujanic

T

Tanzina Chowdhury

M

Maureen J O’Sullivan

R

Ronald R. de Krijger

Princess Máxima Center for Pediatric Oncology

M

Michael R. Stratton

K

Kathy Pritchard-Jones

J

J. Ciaran Hutchinson

J

Jarno Drost

S

Sam Behjati

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