Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wilms' tumour is a paediatric kidney cancer which, in a substantial number of cases, has been associated with a genetic predisposition. Susceptibility to Wilms' tumour can be manifested by the presence of bilateral tumours, and in rare cases by a family history of this tumour or by associated congenital malformations. Like retinoblastoma, Wilms' tumour has been postulated to result from the inactivation of a tumour suppressor gene, although genetic studies implicate more than a single genetic locus. The recent isolation of the WT1 gene, which maps to chromosome 11, band p13, has provided the first molecular clue to Wilms' tumorigenesis. WT1 is specifically inactivated in a number of Wilms' tumours, and mutations have been found in the germline of susceptible individuals. This gene appears to encode a transcription factor with complex alternative splices, whose expression is strictly regulated in the developing kidney. Functional studies will be required to elucidate the role of WT1 in normal kidney development and in tumorigenesis.
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PMID:Role of the WT1 gene in Wilms' tumour. 132 41

A series of 34 Wilms' tumours have been analysed for abnormal expression of the tumour suppressor gene p53 using frozen section immunohistochemistry. All tumours showed immunoreactivity with at least one of the specific antibodies used (monoclonal antibody PAb240, polyclonal antibodies CM1 and JG8). Abnormalities of p53 expression are very frequent in this type of childhood tumour.
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PMID:Aberrant expression of the tumour suppressor gene p53 is very frequent in Wilms' tumours. 133 42

The types of malignancy reported in carriers of constitutional ring chromosomes r(11), r(13), and r(22) are concordant with the chromosomal assignment of tumour suppressor loci associated with Wilms' tumour, retinoblastoma, and meningioma. It is suggested that the somatic instability of ring chromosomes may play a role in this association and that constitutional ring chromosomes may be a source for mapping of tumour suppressor loci with the potential for covering most or all of the human genome. The hypothesis predicts the presence of a locus on chromosome 10 associated with follicular carcinoma of the thyroid, in line with previous cytogenetic findings of rearrangements involving chromosome 10 in thyroid tumours, and a locus on chromosome 22 associated with testicular cancer. Development of neurofibromatoses (NF) that do not fulfil the clinical criteria of neurofibromatosis type 2 (NF2) in carriers with r(22) suggests either the presence of an additional NF locus on chromosome 22 or that ring chromosome mediated predisposition to somatic mutation of a specific tumour suppressor may be associated with atypical development of features usually associated with germline mutations.
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PMID:Constitutional ring chromosomes and tumour suppressor genes. 133 57

Wilms' tumour (WT), aniridia, genitourinary abnormalities and mental retardation form a symptom group (WAGR syndrome) associated with hemizygous deletions of DNA in chromosome band 11p13 (refs 1,2). However, it has not been clear whether hemizygosity at a single locus contributes to more than one phenotype. The tumour suppressor gene for Wilms' tumour, WT1, has been characterized: it is expressed at high levels in the glomeruli of the kidney, as well as the gonadal ridge of the developing gonad, the Sertoli cells of the testis and the epithelial and granulosa cells of the ovary, suggesting a developmental role in the genital system in addition to the kidney. We now report constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities as evidence of a role for a recessive oncogene in mammalian development.
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PMID:WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour. 165 25

Oncogenesis results from an accumulation of genetic mutations in a single cell. Mutations may result in the cell acquiring new functions or losing specific functions required for normal growth control. Evidence for the latter may be adduced from the results of fusing tumour and normal cells to form somatic cell hybrids, and from studies of allele loss in a number of human tumours. The locations the critical genes have been discerned in some cancer predisposition syndromes either by observations of consistent cytogenetic abnormalities, or by genetic linkage studies, or both. Genes whose inactivation is important in the genesis of retinoblastoma, Wilms' tumour and colorectal cancer have been identified and cloned. Their normal functions include control of transcription and cell-cell interactions. In the case of retinoblastoma, the interaction between the normal gene product and that of the transforming genes of a number of oncogenic DNA viruses has been delineated. Identification of 'tumour suppressor' genes has not only improved understanding of the process of oncogenesis, but may also aid in the presymptomatic detection of mutant gene carriers.
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PMID:Recessive oncogenes, antioncogenes and tumour suppression. 186 44

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.
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PMID:Wilms' tumour as a paradigm for the relationship of cancer to development. 196 78

Wilms' tumour is an embryonic kidney tumour thought to arise through aberrant mesenchymal stem cell differentiation and to result from loss of function of a 'tumour suppressor' gene(s). Both sporadic and syndrome-associated Wilms' tumours are accompanied by an increased frequency of abnormalities of the urinary tract and genitalia. Deletional analysis of individuals with the WAGR syndrome (for, Wilms' tumour, aniridia, genitourinary abnormalities and mental retardation) showed that a Wilms' tumour gene lies at chromosomal position 11p13. This led to the isolation of a candidate Wilms' tumour gene, encoding a zinc-finger protein which is likely to be a transcription factor. To gain insight into the role of this candidate gene in normal development and tumorigenesis, we have now performed in situ messenger RNA hybridization on sections of human embryos and Wilms' tumours. The candidate Wilms' tumour gene is expressed specifically in the condensed mesenchyme, renal vesicle and glomerular epithelium of the developing kidney, in the related mesonephric glomeruli and in cells approximating these structures in tumours. The other main sites of expression are the genital ridge, fetal gonad and mesothelium. These data suggest that (1) this candidate is indeed a Wilms' tumour gene, (2) the associated genital abnormalities are pleiotropic effects of mutation in the Wilms' tumour gene itself, in support of recent genetic analysis, and (3) this gene has a specific role in kidney development and a wider role in mesenchymal-epithelial transitions.
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PMID:The candidate Wilms' tumour gene is involved in genitourinary development. 216 59

The technique of somatic cell hybridization has established the phenomenon of tumour suppression and provided evidence for a genetic basis for suppression. Further refinements aimed at eventually identifying 'tumour suppressor' genes include the use of monochromosome transfer via microcell hybridization. The application of this technique to the study of tumour suppression in tumorigenic HeLa cell x fibroblast hybrids, Wilms' tumour, retinoblastoma and osteosarcoma cells is described. The issue of whether tumour suppression involves a direct effect on expression of activated oncogenes is discussed. Transformation of normal human cells in culture by activated cellular oncogenes is an extremely rare event. This may be due to a relatively greater genomic stability of human cells compared to rodent cells. We describe the use of a spontaneously immortalized human keratinocyte cell line, HaCaT, for studies of the effects of introduction of activated c-Ha-ras oncogene into these cells, with particular reference to tumorigenic conversion.
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PMID:A genetic basis for tumour suppression. 254 19

Wilms' tumour is an embryonal kidney tumour which exists in an hereditary and sporadic form. Apart from its obvious importance as a model for renal development and differentiation, the tumour has recently been exploited as an example of the action of tumour suppressor genes (or anti-oncogenes). The latter genes are characterised by a somatic loss of genetic information in tumour development, specifically from the short arm of human chromosome 11 in Wilms' tumour. To further study the developmental aspects of the tumour we have established in vitro cell cultures from tumour tissues, which, unlike the majority of Wilms' tumour cell lines, have been genotyped according to their chromosome 11 gene status and their antigen expression patterns, compared to the original normal kidney and tumour tissues. The cell cultures exist both as primary and secondary cultures, and their limited life span in culture has been extended by transfection of SV40 large T antigen. The mechanism of tumour suppression by the Wilms' locus has been explored by producing cell hybrids between the immortalised kidney cells, and an "indicator cell" (HeLa), whose chromosome 11 genotypes have been monitored in vivo and in vitro by restriction fragment length polymorphisms. Non-random patterns of inheritance of the mutant allele have also been investigated, both in tumour tissue and in syndromes, like the Beckwith-Wiedemann Syndrome, which pre-dispose to development of Wilms' tumour (and other embryonal tumours). It is also apparent that allele-specific methylation occurs in Wilms' tumour tissues, probably resulting in changes of gene expression patterns. Significant elevation of transcription of the N-myc oncogene was detected in the blastemal cells of the most malignant Wilms' tumours, whereas a marked decrease in the expression of HLA class I, at both RNA and protein levels was observed in the same cells. Wilm's tumour provides a clear illustration of the requirement for a combination of dominantly and recessively acting genes, in order to produce a malignant embryonal tumour.
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PMID:Molecular and cellular biology of Wilms' tumour. 255 71

Wilms tumour (WT) is a developmental anomaly of the kidney which results from loss of function of at least one so called tumour suppressor gene on chromosome 11. The position of the gene at chromosome 11p13 is known through the association of WT with aniridia (lack of an iris), mental retardation and genitourinary abnormalities in the WAGR syndrome. Here we discuss the high resolution mapping studies to locate the position of the gene and conclude that the gonadal abnormalities in WAGR patients may be due to a defect in the WT gene itself. In support of this role in genitourinary development we show that a candidate WT gene is expressed in specific regions of the developing kidney and in fetal and embryonic gonads.
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PMID:Wilms tumour: a developmental anomaly. 256 79


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