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^*

^*Corresponding author for this work

Cancer and Genomic Sciences

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1247-1251
Number of pages	5
Journal	Science
Volume	366
Issue number	6470
DOIs	https://doi.org/10.1126/science.aax1323
Publication status	Published - 6 Dec 2019

Bibliographical note

Funding Information:
Funding: This project was principally funded by the Little Princess Trust, the St. Baldrick's Foundation (Robert J. Arceci International Award to S.B.), and Wellcome (fellowship to S.B.; Sanger core funding). Additional funding was received from CRUK (IMPORT study; fellowship to T.J.M.; Cambridge Centre), NIHR (Biomedical Research Centre Great Ormond Street; Cambridge Human Research Tissue Bank; Oxford Biomedical Research Centre; fellowship to T.R.W.O.), the Royal College of Surgeons of England (fellowship to T.J.M.), Wellcome (fellowship to T.H.H.C. and K.S.), Great Ormond Street Hospital Children's Charity (R.A.-S., K.P.-J.), and Li Ka Shing foundation (D.C.W.). J.D. acknowledges funding from the Alpe d'HuZes foundation/KWF Dutch Cancer Society Bas Mulder Award (#10218) and the Oncode Institute.

Publisher Copyright:
Copyright © 2019 The Authors.

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General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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{abad1ab727d345f88900c8780be11a02,

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.",

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 = "Funding Information: Funding: This project was principally funded by the Little Princess Trust, the St. Baldrick's Foundation (Robert J. Arceci International Award to S.B.), and Wellcome (fellowship to S.B.; Sanger core funding). Additional funding was received from CRUK (IMPORT study; fellowship to T.J.M.; Cambridge Centre), NIHR (Biomedical Research Centre Great Ormond Street; Cambridge Human Research Tissue Bank; Oxford Biomedical Research Centre; fellowship to T.R.W.O.), the Royal College of Surgeons of England (fellowship to T.J.M.), Wellcome (fellowship to T.H.H.C. and K.S.), Great Ormond Street Hospital Children's Charity (R.A.-S., K.P.-J.), and Li Ka Shing foundation (D.C.W.). J.D. acknowledges funding from the Alpe d'HuZes foundation/KWF Dutch Cancer Society Bas Mulder Award (#10218) and the Oncode Institute. Publisher Copyright: Copyright {\textcopyright} 2019 The Authors.",

year = "2019",

month = dec,

day = "6",

doi = "10.1126/science.aax1323",

language = "English",

volume = "366",

pages = "1247--1251",

journal = "Science",

issn = "0036-8075",

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, no. 6470, pp. 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

N1 - Funding Information: Funding: This project was principally funded by the Little Princess Trust, the St. Baldrick's Foundation (Robert J. Arceci International Award to S.B.), and Wellcome (fellowship to S.B.; Sanger core funding). Additional funding was received from CRUK (IMPORT study; fellowship to T.J.M.; Cambridge Centre), NIHR (Biomedical Research Centre Great Ormond Street; Cambridge Human Research Tissue Bank; Oxford Biomedical Research Centre; fellowship to T.R.W.O.), the Royal College of Surgeons of England (fellowship to T.J.M.), Wellcome (fellowship to T.H.H.C. and K.S.), Great Ormond Street Hospital Children's Charity (R.A.-S., K.P.-J.), and Li Ka Shing foundation (D.C.W.). J.D. acknowledges funding from the Alpe d'HuZes foundation/KWF Dutch Cancer Society Bas Mulder Award (#10218) and the Oncode Institute. Publisher Copyright: Copyright © 2019 The Authors.

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.

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U2 - 10.1126/science.aax1323

DO - 10.1126/science.aax1323

M3 - Article

C2 - 31806814

AN - SCOPUS:85076312335

SN - 0036-8075

VL - 366

SP - 1247

EP - 1251

JO - Science

JF - Science

IS - 6470

ER -

Embryonal precursors of Wilms tumor

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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