| Literature DB >> 31806814 |
Tim H H Coorens1, Taryn D Treger1,2,3, Reem Al-Saadi4,5, Luiza Moore1,2, Maxine G B Tran6,7, Thomas J Mitchell1,2,8, Suzanne Tugnait4, Christine Thevanesan4, Matthew D Young1, Thomas R W Oliver1,2,9, Minou Oostveen4,5, Grace Collord1,2,3, Patrick S Tarpey2, Alex Cagan1, Yvette Hooks1, Mark Brougham10, Ben C Reynolds11, Giuseppe Barone5, John Anderson4,5, Mette Jorgensen5, G A Amos Burke2,3, Johannes Visser2, James C Nicholson2,3, Naima Smeulders5, Imran Mushtaq5, Grant D Stewart2,8, Peter J Campbell1, David C Wedge12,13, Iñigo Martincorena1, Dyanne Rampling5, Liz Hook2,9, Anne Y Warren2,9, Nicholas Coleman2,9, Tanzina Chowdhury5, Neil Sebire4,5, Jarno Drost14, Kourosh Saeb-Parsy2,8, Michael R Stratton1, Karin Straathof4,5, Kathy Pritchard-Jones4,5, Sam Behjati15,2,3.
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.Entities:
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Year: 2019 PMID： 31806814 PMCID： PMC6914378 DOI： 10.1126/science.aax1323
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728