Open AccessDeducing the stage of origin of Wilms' tumours from a developmental series of Wt1 mutants
Author(s) -
Rachel L. Berry,
Derya D. Ozdemir,
Bruce J. Aronow,
Nils O. Lindström,
Tatiana Dudnakova,
Anna Thornburn,
Paul Perry,
Richard Baldock,
Chris Armit,
Anagha Joshi,
Marc Jeanpierre,
Jingdong Shan,
Seppo Vainio,
James Baily,
David G. Brownstein,
Jamie A. Davies,
Nicholas D. Hastie,
Peter Hohenstein
Publication year - 2015
Publication title -
disease models and mechanisms
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.327
H-Index - 83
eISSN - 1754-8411
pISSN - 1754-8403
DOI - 10.1242/dmm.018523
Subject(s) - biology , mutant , wilms tumour , wilms' tumor , nephron , suppressor , phenotype , kidney development , stage (stratigraphy) , cancer research , developmental stage , gene , kidney , genetics , embryonic stem cell , psychology , paleontology , developmental psychology
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.