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Embryonal precursors of Wilms tumor.

Authors:
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

Science 2019 12;366(6470):1247-1251

Wellcome Sanger Institute, Hinxton CB10 1SA, UK.

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 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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http://dx.doi.org/10.1126/science.aax1323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914378PMC
December 2019

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