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

Research output: Contribution to journalArticlepeer-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 languageEnglish
Pages (from-to)1247-1251
Number of pages5
JournalScience
Volume366
Issue number6470
DOIs
Publication statusPublished - 6 Dec 2019

Keywords

  • Child
  • Clone Cells
  • DNA Methylation
  • Humans
  • Kidney/embryology
  • Kidney Neoplasms/genetics
  • Mutation
  • Phylogeny
  • Precancerous Conditions/pathology
  • Wilms Tumor/genetics

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