High resolution clonal architecture of hypomutated Wilms tumours

Henry Lee-Six; Taryn D. Treger; Manas Dave; Tim H.H. 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

doi:10.1038/s41467-025-59854-4

High resolution clonal architecture of hypomutated Wilms tumours

Henry Lee-Six
, Taryn D. Treger
, Manas Dave
, Tim H.H. 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

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

1 Citaat (Scopus)

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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.

Originele taal-2	Engels
Artikelnummer	4647
Tijdschrift	Nature communications
Volume	16
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s41467-025-59854-4
Status	Gepubliceerd - 29 mei 2025

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10.1038/s41467-025-59854-4

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Lee-Six, H., Treger, T. D., Dave, M., Coorens, T. H. H., Anderson, N. D., Tiersma, Y., Derakhshan, S., de Haan, S., van den Heuvel-Eibrink, M. M., Wang, Y., Wenger, A., Al-Saadi, R., Lawford, A., Letunovska, A., Wegert, J., Parks, C., Morcrette, G., Gessler, M., Vujanic, G., ... Behjati, S. (2025). High resolution clonal architecture of hypomutated Wilms tumours. Nature communications, 16(1), Artikel 4647. https://doi.org/10.1038/s41467-025-59854-4

@article{1250152cb9534c94a0468ab75d5861c7,

title = "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 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.",

keywords = "Kidney Neoplasms/genetics, Humans, Child, Preschool, Male, Female, High-Throughput Nucleotide Sequencing, Mutation, Wilms Tumor/genetics, Child, Clonal Evolution/genetics",

author = "Henry Lee-Six and Treger, \{Taryn D.\} and Manas Dave and Coorens, \{Tim H.H.\} and Anderson, \{Nathaniel D.\} and Yvonne Tiersma and Sepide Derakhshan and \{de Haan\}, Sanne and \{van den Heuvel-Eibrink\}, \{Marry M.\} and Yichen Wang and Anna Wenger and Reem Al-Saadi and Alice Lawford and Aleksandra Letunovska and Jenny Wegert and Conor Parks and Guillaume Morcrette and Manfred Gessler and Gordan Vujanic and Tanzina Chowdhury and \{J O{\textquoteright}Sullivan\}, Maureen and \{de Krijger\}, \{Ronald R.\} and Stratton, \{Michael R.\} and Kathy Pritchard-Jones and Hutchinson, \{J. Ciaran\} and Jarno Drost and Sam Behjati",

note = "{\textcopyright} 2025. The Author(s).",

year = "2025",

month = may,

day = "29",

doi = "10.1038/s41467-025-59854-4",

language = "English",

volume = "16",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Lee-Six, H, Treger, TD, Dave, M, Coorens, THH, Anderson, ND, Tiersma, Y, Derakhshan, S, de Haan, S, van den Heuvel-Eibrink, MM, Wang, Y, Wenger, A, Al-Saadi, R, Lawford, A, Letunovska, A, Wegert, J, Parks, C, Morcrette, G, Gessler, M, Vujanic, G, Chowdhury, T, J O’Sullivan, M, de Krijger, RR, Stratton, MR, Pritchard-Jones, K, Hutchinson, JC, Drost, J & Behjati, S 2025, 'High resolution clonal architecture of hypomutated Wilms tumours', Nature communications, vol. 16, nr. 1, 4647. https://doi.org/10.1038/s41467-025-59854-4

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AU - Lee-Six, Henry

AU - Treger, Taryn D.

AU - Dave, Manas

AU - Coorens, Tim H.H.

AU - Anderson, Nathaniel D.

AU - Tiersma, Yvonne

AU - Derakhshan, Sepide

AU - de Haan, Sanne

AU - van den Heuvel-Eibrink, Marry M.

AU - Wang, Yichen

AU - Wenger, Anna

AU - Al-Saadi, Reem

AU - Lawford, Alice

AU - Letunovska, Aleksandra

AU - Wegert, Jenny

AU - Parks, Conor

AU - Morcrette, Guillaume

AU - Gessler, Manfred

AU - Vujanic, Gordan

AU - Chowdhury, Tanzina

AU - J O’Sullivan, Maureen

AU - de Krijger, Ronald R.

AU - Stratton, Michael R.

AU - Pritchard-Jones, Kathy

AU - Hutchinson, J. Ciaran

AU - Drost, Jarno

AU - Behjati, Sam

PY - 2025/5/29

Y1 - 2025/5/29

N2 - 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.

AB - 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.

KW - Kidney Neoplasms/genetics

KW - Humans

KW - Child, Preschool

KW - Male

KW - Female

KW - High-Throughput Nucleotide Sequencing

KW - Mutation

KW - Wilms Tumor/genetics

KW - Child

KW - Clonal Evolution/genetics

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DO - 10.1038/s41467-025-59854-4

M3 - Article

C2 - 40442086

AN - SCOPUS:105006897669

SN - 2041-1723

VL - 16

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 4647

ER -

High resolution clonal architecture of hypomutated Wilms tumours

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