Altered trans-activational properties of a mutated WT1 gene product in a WAGR-associated Wilms' tumor.
Cancer Res
; 53(20): 4757-60, 1993 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-8402654
ABSTRACT
WAGR syndrome is an acronym for a rare constellation of congenital abnormalities including predisposition to Wilms' tumor, Aniridia, Genitourinary malformations, and mental Retardation. These congenital defects are associated with a constitutional deletion affecting one copy of chromosome band 11p13, implicating the loss of one allele from a number of contiguous genes in this syndrome. Predisposition to Wilms' tumor and genitourinary abnormalities have been attributed to hemizygosity for the WT1 tumor suppressor gene, a transcriptional repressor that is normally expressed transiently during kidney development. Here we show that a Wilms' tumor arising in a child with WAGR syndrome contained a point mutation within the remaining WT1 allele. This mutation resulted in a glycine to aspartic acid substitution within the putative trans-activation domain of WT1, converting the encoded protein from a transcriptional repressor to an activator of its target DNA sequence. Thus, a critical amino acid substitution can alter the functional properties of WT1 and provide the "second hit" required for Wilms tumorigenesis.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cromosomas Humanos Par 11
/
Genes Supresores de Tumor
/
Mutación Puntual
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Síndrome WAGR
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Tumor de Wilms
/
Proteínas de Unión al ADN
/
Riñón
/
Neoplasias Renales
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Año:
1993
Tipo del documento:
Article