Embryonal precursors of Wilms tumor

T.H.H. Coorens; T.D. Treger; R. Al-Saadi; L. Moore; M.G.B. Tran; T.J. Mitchell; S. Tugnait; C. Thevanesan; M.D. Young; T.R.W. Oliver; M. Oostveen; G. Collord; P.S. Tarpey; A. Cagan; Y. Hooks; M. Brougham; B.C. Reynolds; G. Barone; J. Anderson; M. Jorgensen; G.A.A. Burke; J. Visser; J.C. Nicholson; N. Smeulders; I. Mushtaq; G.D. Stewart; P.J. Campbell; D.C. Wedge; I. Martincorena; D. Rampling; L. Hook; A.Y. Warren; N. Coleman; T. Chowdhury; N. Sebire; J. Drost; K. Saeb-Parsy; M.R. Stratton; K. Straathof; K. Pritchard-Jones; S. Behjati

doi:10.1126/science.aax1323

Embryonal precursors of Wilms tumor

T.H.H. Coorens, T.D. Treger, R. Al-Saadi, L. Moore, M.G.B. Tran, T.J. Mitchell, S. Tugnait, C. Thevanesan, M.D. Young, T.R.W. Oliver, M. Oostveen, G. Collord, P.S. Tarpey, A. Cagan, Y. Hooks, M. Brougham, B.C. Reynolds, G. Barone, J. Anderson, M. JorgensenG.A.A. Burke, J. Visser, J.C. Nicholson, N. Smeulders, I. Mushtaq, G.D. Stewart, P.J. Campbell, D.C. Wedge, I. Martincorena, D. Rampling, L. Hook, A.Y. Warren, N. Coleman, T. Chowdhury, N. Sebire, J. Drost, K. Saeb-Parsy, M.R. Stratton, K. Straathof, K. Pritchard-Jones, S. Behjati

Division of Cancer Sciences (L5)

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
Journal	Science
DOIs	https://doi.org/10.1126/science.aax1323
Publication status	Published - 6 Dec 2019

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

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

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10.1126/science.aax1323

https://discovery.ucl.ac.uk/id/eprint/10088097/

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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. https://doi.org/10.1126/science.aax1323

@article{ace7581698b24073a403d4f33d87a428,

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 = "T.H.H. Coorens and T.D. Treger and R. Al-Saadi and L. Moore and M.G.B. Tran and T.J. Mitchell and S. Tugnait and C. Thevanesan and M.D. Young and T.R.W. Oliver and M. Oostveen and G. Collord and P.S. Tarpey and A. Cagan and Y. Hooks and M. Brougham and B.C. Reynolds and G. Barone and J. Anderson and M. Jorgensen and G.A.A. Burke and J. Visser and J.C. Nicholson and N. Smeulders and I. Mushtaq and G.D. Stewart and P.J. Campbell and D.C. Wedge and I. Martincorena and D. Rampling and L. Hook and A.Y. Warren and N. Coleman and T. Chowdhury and N. Sebire and J. Drost and K. Saeb-Parsy and M.R. Stratton and K. Straathof and K. Pritchard-Jones and S. Behjati",

year = "2019",

month = dec,

day = "6",

doi = "10.1126/science.aax1323",

language = "English",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science (A A A S)",

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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. https://doi.org/10.1126/science.aax1323

TY - JOUR

T1 - Embryonal precursors of Wilms tumor

AU - Coorens, T.H.H.

AU - Treger, T.D.

AU - Al-Saadi, R.

AU - Moore, L.

AU - Tran, M.G.B.

AU - Mitchell, T.J.

AU - Tugnait, S.

AU - Thevanesan, C.

AU - Young, M.D.

AU - Oliver, T.R.W.

AU - Oostveen, M.

AU - Collord, G.

AU - Tarpey, P.S.

AU - Cagan, A.

AU - Hooks, Y.

AU - Brougham, M.

AU - Reynolds, B.C.

AU - Barone, G.

AU - Anderson, J.

AU - Jorgensen, M.

AU - Burke, G.A.A.

AU - Visser, J.

AU - Nicholson, J.C.

AU - Smeulders, N.

AU - Mushtaq, I.

AU - Stewart, G.D.

AU - Campbell, P.J.

AU - Wedge, D.C.

AU - Martincorena, I.

AU - Rampling, D.

AU - Hook, L.

AU - Warren, A.Y.

AU - Coleman, N.

AU - Chowdhury, T.

AU - Sebire, N.

AU - Drost, J.

AU - Saeb-Parsy, K.

AU - Stratton, M.R.

AU - Straathof, K.

AU - Pritchard-Jones, K.

AU - Behjati, S.

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.

U2 - 10.1126/science.aax1323

DO - 10.1126/science.aax1323

M3 - Article

SN - 0036-8075

JO - Science

JF - Science

ER -

Embryonal precursors of Wilms tumor

Abstract

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