Bilateral Wilms tumor and early presentation in pediatric patients is associated with the truncation of the Wilms tumor 1 protein.
J Pediatr
; 163(1): 224-9, 2013 Jul.
Article
en En
| MEDLINE
| ID: mdl-23403252
ABSTRACT
OBJECTIVES:
To investigate the frequency of constitutional Wilms tumor 1 gene (WT1) abnormalities in children with bilateral Wilms tumor (WT) and the age of tumor onset in patients with a mutation. STUDYDESIGN:
Eight patients with bilateral WT were studied. High-resolution melting and direct sequencing were used to screen for the WT1 gene. Western blotting was performed to determine whether the identified mutations were associated with expressed truncated WT1 protein.RESULTS:
The median age of tumor onset in patients with a mutation in the WT1 was lower (10 months) than in those without a mutation (39 months). Three novel heterozygous nonsense mutations were identified in exon 8 in peripheral blood from 3 individuals, whereas all 3 tumor tissues lacked the wild-type allele. All mutations led to a premature stop codon with truncation of the WT1 protein. In 1 patient, a truncated form of WT1 protein was identified, suggesting that development of the WT may have resulted from expression of an abnormal protein. Four distinct silent single-nucleotide polymorphisms (SNPs) were detected. All 3 patients with a pathogenic WT1 mutation had 2 synonymous SNPs, whereas only 1 of the remaining 5 patients had a single synonymous SNP (P < .05).CONCLUSIONS:
Bilateral WT are associated with early presentation in pediatric patients and a high frequency of WT1 nonsense mutations in exon 8. Silent SNPs may also be involved in the development of WT.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Genes del Tumor de Wilms
/
Tumor de Wilms
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Proteínas WT1
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Neoplasias Renales
/
Mutación
Tipo de estudio:
Risk_factors_studies
Límite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
J Pediatr
Año:
2013
Tipo del documento:
Article
País de afiliación:
Australia