Repository logo
 

Embryonal precursors of Wilms tumor

Accepted version
Peer-reviewed

No Thumbnail Available

Type

Article

Change log

Authors

Mitchell, Thomas 
Behjati, Sam 

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.

Description

Keywords

Journal Title

Science

Conference Name

Journal ISSN

Volume Title

Publisher

American Association for the Advancement of Science

Rights

All rights reserved
Sponsorship
Wellcome, CRUK, NIHR