Deducing the stage of origin of Wilms' tumours from a developmental series of Wt1-mutant mice

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 with human tumour material of mutant or wild-type WT1 datasets identified 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.

DOI: 10.1242/dmm.018523

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Cite this paper

@inproceedings{Berry2015DeducingTS, title={Deducing the stage of origin of Wilms' tumours from a developmental series of Wt1-mutant mice}, author={Rachel L. Berry and Derya D. Ozdemir and Bruce Aronow and Nils O. Lindstr{\"{o}m and Tatiana Dudnakova and Anna Thornburn and Paul Perry and Richard Baldock and Chris Armit and Anagha Joshi and C{\'e}cile Jeanpierre and Jingdong Shan and Seppo Vainio and James Baily and David Brownstein and Jamie Davies and Nicholas D. Hastie and Peter Hohenstein}, booktitle={Disease models & mechanisms}, year={2015} }