Wilms' tumour as a paradigm for the relationship of cancer to development

Wilms' tumour or nephroblastoma is one of the commonest solid paediatric malignant diseases, accounting for 8% of childhood cancers. The tumour arises through aberrant differentiation of metanephric mesenchyme and thus represents a paradigm for the relationship of cancer and development. There is considerable heterogeneity in the pathology of Wilms' tumour and several genes have been implicated in its aetiology. One of these genes, located at chromosome 11p13, is categorised as a 'tumour suppressor' gene since loss of function can lead to malignancy. It has not been possible as yet to correlate the involvement of a particular locus with a subset of tumour pathology. The recently cloned Wilms' tumour gene encodes a putative transcription factor which is likely to activate or repress the expression of other genes in kidney development. We have shown by in situ hybridization that expression of this gene is restricted to specific cell types within the developing kidney. It is also expressed in a limited range of embryonic tissues, including the gonad, spleen and mesothelium. With the benefit of this new information, we speculate on the part played by this gene in normal kidney development, in tumorigenesis and in other aspects of Wilms' tumour; these include associated congenital abnormalities, genetic predisposition to second tumours and inheritance of Wilms' tumour.