Absence of germline and somatic p53 alterations in children with sporadic brain tumors.
J Neurooncol
; 52(3): 227-35, 2001 May.
Article
em En
| MEDLINE
| ID: mdl-11519852
ABSTRACT
Cancers of the central nervous system are the most common solid tumors of childhood. Although somatic alterations of the p53 tumor suppressor gene have been implicated in brain tumorigenesis, the role of germline p53 mutations in the development of childhood brain tumors has not been well defined. As a component of an ongoing extensive study of the epidemiology of childhood brain tumors, we prospectively examined the germline and tumor p53 gene status in 85 children without a family history of cancer who were diagnosed with a sporadic malignant central nervous system tumor. Using PCR/single-strand conformational polymorphism analysis and direct DNA sequencing, 85 children were screened for the presence of constitutional p53 sequence alterations in exons 2 and 4 through 11. No mutations were identified. Commonly reported sequence polymorphisms were observed at codon 72, as well as in 2 other previously described nucleotide residues. Forty-four brain tumor samples were available for analysis and of these 40 were paired with peripheral blood. Once again, no p53 mutations were found. Of the 5 germline samples with the 2 common polymorphisms, only one had a paired tumor sample for comparison and the tumor contained the same alteration as the germline. Of note, one tumor, a PNET of the cerebellum (medulloblastoma), showed loss of heterozygosity at codon 72. We can conclude that the frequency of germline and somatic p53 mutations in sporadic childhood brain tumors is very low, probably less than 1%, and there is no need to screen these patients routinely for their germline p53 status. However, the potential significance of LOH at codon 72 remains to be elucidated.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
/
Genes p53
/
Mutação em Linhagem Germinativa
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Child
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Child, preschool
/
Humans
/
Infant
Idioma:
En
Revista:
J Neurooncol
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Canadá