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Deducing the stage of origin of Wilms tumours from a developmental series of Wt1 mutants

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Original languageEnglish
Pages (from-to)903-17
Number of pages15
JournalDisease Models & Mechanisms
Volume8
Issue number8
Early online date14 May 2015
DOIs
Publication statusPublished - Aug 2015

Abstract

Wilms' tumours, paediatric kidney cancers, are the archetypal example of tumours caused through the disruption of normal development. The genetically best defined subgroup of Wilms' tumours is the group caused by biallelic loss of the WT1 tumour suppressor gene. Here we describe a developmental series of mouse models with conditional loss of Wt1 in different stages of nephron development before and after the mesenchymal to epithelial transition (MET). We demonstrate that Wt1 is essential for normal development at all kidney developmental stages under study. Comparison of genome-wide expression data from the mutant mouse models to human tumour material of WT1-mutant and WT1 wild-type datasets identifies the stage of origin of human WT1-mutant tumours, and emphasizes fundamental differences between the two human tumour groups due to different developmental stages of origin.

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