Embryonal precursors of Wilms tumor

Tim H H Coorens; Taryn D Treger; Reem Al-Saadi; Luiza Moore; Maxine G B Tran; Thomas J Mitchell; Suzanne Tugnait; Christine Thevanesan; Matthew D Young; Thomas R W Oliver; Minou Oostveen; Grace Collord; Patrick S Tarpey; Alex Cagan; Yvette Hooks; Mark Brougham; Ben C Reynolds; Giuseppe Barone; John Anderson; Mette Jorgensen; G A Amos Burke; Johannes Visser; James C Nicholson; Naima Smeulders; Imran Mushtaq; Grant D Stewart; Peter J Campbell; David C Wedge; Iñigo Martincorena; Dyanne Rampling; Liz Hook; Anne Y Warren; Nicholas Coleman; Tanzina Chowdhury; Neil Sebire; Jarno Drost; Kourosh Saeb-Parsy; Michael R Stratton; Karin Straathof; Kathy Pritchard-Jones; Sam Behjati

doi:10.1126/science.aax1323

Embryonal precursors of Wilms tumor

Tim H H Coorens, Taryn D Treger, Reem Al-Saadi, Luiza Moore, Maxine G B Tran, Thomas J Mitchell, Suzanne Tugnait, Christine Thevanesan, Matthew D Young, Thomas R W Oliver, Minou Oostveen, Grace Collord, Patrick S Tarpey, Alex Cagan, Yvette Hooks, Mark Brougham, Ben C Reynolds, Giuseppe Barone, John Anderson, Mette JorgensenG A Amos Burke, Johannes Visser, James C Nicholson, Naima Smeulders, Imran Mushtaq, Grant D Stewart, Peter J Campbell, David C Wedge, Iñigo Martincorena, Dyanne Rampling, Liz Hook, Anne Y Warren, Nicholas Coleman, Tanzina Chowdhury, Neil Sebire, Jarno Drost, Kourosh Saeb-Parsy, Michael R Stratton, Karin Straathof, Kathy Pritchard-Jones, Sam Behjati

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Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the H19 locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.

Originele taal-2	Engels
Pagina's (van-tot)	1247-1251
Aantal pagina's	5
Tijdschrift	Science
Volume	366
Nummer van het tijdschrift	6470
DOI's	https://doi.org/10.1126/science.aax1323
Status	Gepubliceerd - 6 dec. 2019

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10.1126/science.aax1323

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Coorens, T. H. H., Treger, T. D., Al-Saadi, R., Moore, L., Tran, M. G. B., Mitchell, T. J., Tugnait, S., Thevanesan, C., Young, M. D., Oliver, T. R. W., Oostveen, M., Collord, G., Tarpey, P. S., Cagan, A., Hooks, Y., Brougham, M., Reynolds, B. C., Barone, G., Anderson, J., ... Behjati, S. (2019). Embryonal precursors of Wilms tumor. Science, 366(6470), 1247-1251. https://doi.org/10.1126/science.aax1323

@article{2f11b5cabb2e4fc29d9b62ee0c44535c,

title = "Embryonal precursors of Wilms tumor",

abstract = "Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the H19 locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.",

keywords = "Child, Clone Cells, DNA Methylation, Humans, Kidney/embryology, Kidney Neoplasms/genetics, Mutation, Phylogeny, Precancerous Conditions/pathology, Wilms Tumor/genetics",

author = "Coorens, {Tim H H} and Treger, {Taryn D} and Reem Al-Saadi and Luiza Moore and Tran, {Maxine G B} and Mitchell, {Thomas J} and Suzanne Tugnait and Christine Thevanesan and Young, {Matthew D} and Oliver, {Thomas R W} and Minou Oostveen and Grace Collord and Tarpey, {Patrick S} and Alex Cagan and Yvette Hooks and Mark Brougham and Reynolds, {Ben C} and Giuseppe Barone and John Anderson and Mette Jorgensen and Burke, {G A Amos} and Johannes Visser and Nicholson, {James C} and Naima Smeulders and Imran Mushtaq and Stewart, {Grant D} and Campbell, {Peter J} and Wedge, {David C} and I{\~n}igo Martincorena and Dyanne Rampling and Liz Hook and Warren, {Anne Y} and Nicholas Coleman and Tanzina Chowdhury and Neil Sebire and Jarno Drost and Kourosh Saeb-Parsy and Stratton, {Michael R} and Karin Straathof and Kathy Pritchard-Jones and Sam Behjati",

note = "Copyright {\textcopyright} 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2019",

month = dec,

day = "6",

doi = "10.1126/science.aax1323",

language = "English",

volume = "366",

pages = "1247--1251",

journal = "Science",

issn = "1095-9203",

publisher = "American Association for the Advancement of Science",

number = "6470",

}

Coorens, THH, Treger, TD, Al-Saadi, R, Moore, L, Tran, MGB, Mitchell, TJ, Tugnait, S, Thevanesan, C, Young, MD, Oliver, TRW, Oostveen, M, Collord, G, Tarpey, PS, Cagan, A, Hooks, Y, Brougham, M, Reynolds, BC, Barone, G, Anderson, J, Jorgensen, M, Burke, GAA, Visser, J, Nicholson, JC, Smeulders, N, Mushtaq, I, Stewart, GD, Campbell, PJ, Wedge, DC, Martincorena, I, Rampling, D, Hook, L, Warren, AY, Coleman, N, Chowdhury, T, Sebire, N, Drost, J, Saeb-Parsy, K, Stratton, MR, Straathof, K, Pritchard-Jones, K & Behjati, S 2019, 'Embryonal precursors of Wilms tumor', Science, vol. 366, nr. 6470, blz. 1247-1251. https://doi.org/10.1126/science.aax1323

TY - JOUR

T1 - Embryonal precursors of Wilms tumor

AU - Coorens, Tim H H

AU - Treger, Taryn D

AU - Al-Saadi, Reem

AU - Moore, Luiza

AU - Tran, Maxine G B

AU - Mitchell, Thomas J

AU - Tugnait, Suzanne

AU - Thevanesan, Christine

AU - Young, Matthew D

AU - Oliver, Thomas R W

AU - Oostveen, Minou

AU - Collord, Grace

AU - Tarpey, Patrick S

AU - Cagan, Alex

AU - Hooks, Yvette

AU - Brougham, Mark

AU - Reynolds, Ben C

AU - Barone, Giuseppe

AU - Anderson, John

AU - Jorgensen, Mette

AU - Burke, G A Amos

AU - Visser, Johannes

AU - Nicholson, James C

AU - Smeulders, Naima

AU - Mushtaq, Imran

AU - Stewart, Grant D

AU - Campbell, Peter J

AU - Wedge, David C

AU - Martincorena, Iñigo

AU - Rampling, Dyanne

AU - Hook, Liz

AU - Warren, Anne Y

AU - Coleman, Nicholas

AU - Chowdhury, Tanzina

AU - Sebire, Neil

AU - Drost, Jarno

AU - Saeb-Parsy, Kourosh

AU - Stratton, Michael R

AU - Straathof, Karin

AU - Pritchard-Jones, Kathy

AU - Behjati, Sam

PY - 2019/12/6

Y1 - 2019/12/6

N2 - Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the H19 locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.

AB - Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the H19 locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.

KW - Child

KW - Clone Cells

KW - DNA Methylation

KW - Humans

KW - Kidney/embryology

KW - Kidney Neoplasms/genetics

KW - Mutation

KW - Phylogeny

KW - Precancerous Conditions/pathology

KW - Wilms Tumor/genetics

UR - http://www.scopus.com/inward/record.url?scp=85076312335&partnerID=8YFLogxK

U2 - 10.1126/science.aax1323

DO - 10.1126/science.aax1323

M3 - Article

C2 - 31806814

SN - 1095-9203

VL - 366

SP - 1247

EP - 1251

JO - Science

JF - Science

IS - 6470

ER -

Embryonal precursors of Wilms tumor

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