The candidate Wilms' tumour gene is involved in genitourinary development

  title={The candidate Wilms' tumour gene is involved in genitourinary development},
  author={Kathryn Pritchard-Jones and Stewart Fleming and Duncan Davidson and Wendy A. Bickmore and David Porteous and Christine M. Gosden and Jonathan B. L. Bard and Alan Buckler and Jerry Pelletier and David E. Housman and Veronica van Heyningen and Nicholas D. Hastie},
WILMS' tumour is an embryonic kidney tumour thought to arise through aberrant mesenchymal stem cell differentiation1 and to result from loss of function of a 'tumour suppressor' gene(s)2. Both sporadic and syndrome-associated Wilms' tumours are accompanied by an increased frequency of abnormalities of the urinary tract and genitalia3. Deletional analysis of individuals with the WAGR syndrome4–8 (for, Wilms' tumour, aniridia, genitourinary abnormalities and mental retardation) showed that a… 

The molecular biology of Wilms tumour.

WT serves as a paradigm for understanding the relationship between loss of developmental control and gain of tumourigenic potential, and some loci have been shown to be associated with particular clinical outcomes, suggesting that they might be used to determine prognosis.

Investigation of the Wilms' tumour suppressor protein (WT1)

The N-terminus of WT1 was investigated to determine the minimal region required for self association, and a functional assay was designed to determined the DNA binding fractional activity of the WT1 zinc finger domain variants used by Fagerlund (2009).

Evolutionary comparison in the vertebrate lineage of WT1, a Wilms' tumour predisposition gene

WTI analysis in Wilms' tumours revealed that both functional copies are lost in about 10% of sporadic Wilm's tumours, confirming the role of WTI as a tumour suppressor gene in at least some cases, following Knudson's two hit hypothesis for tumorigenesis.

The role of Wilms' tumor genes.

  • M. Hirose
  • Medicine, Biology
    The journal of medical investigation : JMI
  • 1999
A correlated expression between WT1 and mdr-1 in vincristine resistant cells indicates a close relation with multi-drug resistance and is a promising diagnostic marker for chemoresistance in hematologic malignancies.

WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour

Constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities are reported as evidence of a role for a recessive oncogene in mammalian development.

Wilms’ tumour - a case of disrupted development

How one of the normal functions of WT1 may be to suppress myogenesis during kidney development is discussed and how YAC (yeast artificial chromosome) transgenesis to analyse WT1 regulation and function in mice is described.

Expression of the Wilms' tumor suppressor gene WT1 during mouse embryogenesis.

In situ mRNA hybridization and immunohistochemistry is used to examine WT1 expression in murine embryos during the period prior to and throughout active organogenesis to better define the temporal and spatial distribution ofWT1 expression during embryogenesis.

Wilms tumor and the WT1 gene.

Understanding the distinct functional properties of WT1 isoforms and tumor-associated variants will provide unique insight into the link between normal organ-specific differentiation and malignancy.


A sensitive immunohistochemical technique was established to localize the WT1 gene product in archival normal tissues and paediatric renal tumour samples, providing an insight into the interrelationships of these renal tumours.



Familial predisposition to Wilms' tumour does not map to the short arm of chromosome 11

A multipoint linkage analysis of a family segregating for Wilms' tumour, using polymorphic DNA markers mapped to chromosome lip implies an aetiological heterogeneity for Wiltshire tumour and raises questions concerning the general applicability of the carcinogenesis model.

The β-subunit of follicle-stimulating hormone is deleted in patients with aniridia and Wilms' tumour, allowing a further definition of the WAGR locus

Close physical linkage between FSHB and the WAGR locus is demonstrated, suggest a gene order for the four deleted markers and exclude other markers tested from this region, as well as testing genomic DNA from the hybrids with chromosome 11-specific probes.

Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping

YTOGENETIC analysis has identified chromosome Ilpl3 as the smallest overlap region for deletions found in individuals with WAGR syndrome, which includes Wilms tumour, anirida, genito-urinary abnormalities and mental retardation.

Lack of linkage of familial Wilms' tumour to chromosomal band 11 p13

Investigating whether familial predisposition to WT is due to a germinal 11p13 mutation, which is distinct from the gene involved in tumorigensis and in WT predisposition in WT/aniridia 11p 13-deletion patients, found that familialWT predisposition was not genetically linked to any of the 11 p13 markers.

Molecular analysis of chromosome 11 deletions in aniridia-Wilms tumor syndrome.

Analysis of DNA from the cell lines and hybrids and with a cloned cDNA probe has shown that the catalase gene is deleted in four of five patients, and it is concluded these genes are likely to be outside the region 11p12-11p15.

Familial Wiedemann-Beckwith syndrome and a second Wilms tumor locus both map to 11p15.5.

Evidence is provided that familial WBS likely results from a defect at the same genetic locus as does its sporadic counterpart, and there is another locus, distinct from that involved in the WAGR syndrome, which plays a role in the association of Wilms tumor with WBS.

Two anonymous DNA segments distinguish the Wilms' tumor and aniridia loci.

Two new anonymous DNA segments have been identified that map to the WAGR region of 11p13 that identify a cytologically undetectable deletion associated with a balanced chromosome translocation inherited by a patient with familial aniridia, but not Wilms' tumor.

Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion.

The genetic heterogeneity of aniridia, the AGR triad, and Wilms' tumor are demonstrated, and Williams' tumor is indicated to be a neoplastic birth defect which can result from a variety of embryologic insults, some of which may be chromosomal or heritable.

Infrequent genomic rearrangement and normal expression of the putative RB1 gene in retinoblastoma tumors.

To extend the characterization of this gene, probes were used to search for genomic rearrang of DNA and to study the expression of the 4.7R gene in RB tumors, osteosarcoma tumors arising in RB patients, and other normal and malignant tissues.