Document Detail


High frequency of TP53 mutations in juvenile pilocytic astrocytomas indicates role of TP53 in the development of these tumors.
MedLine Citation:
PMID:  10416986     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In adults, the TP53 tumor suppressor gene is frequently mutated in astrocytic brain tumors which is supposed to represent an early event in their development. In juvenile pilocytic and low-grade astrocytomas, however, TP53 mutations have until now been reported as rare, which has led to the suggestion that these tumors may follow a different molecular pathogenesis with an involvement of genes other than TP53. Our analysis of 20 pilocytic and two low-grade astrocytomas of childhood, based on a comprehensive denaturing gradient gel electrophoresis (DGGE) mutation detection assay of the entire coding region, including all splice site junctions of TP53, showed mutations considered as causative in 7 of the 20 (35%) pilocytic astrocytomas and in one of the two low-grade astrocytomas. Our finding is significantly different from the mutation frequency of 1.3% (2/155) previously reported for these tumor types. This may be attributed to the mutation detection system used, which also detects mutations occurring outside the evolutionary conserved region of TP53. Our results suggest that, contrary to the present notion, TP53 mutations may well play a role in the development of juvenile astrocytomas. Furthermore, no mutations were found in tumors of patients with progression of residual tumor after postoperative follow-up. This suggests that TP53 mutations may be associated with less aggressive forms of juvenile astrocytomas, analogous to the situation in adult astrocytomas.
Authors:
V M Hayes; C M Dirven; A Dam; E Verlind; W M Molenaar; J J Mooij; R M Hofstra; C H Buys
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain pathology (Zurich, Switzerland)     Volume:  9     ISSN:  1015-6305     ISO Abbreviation:  Brain Pathol.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-09-27     Completed Date:  1999-09-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9216781     Medline TA:  Brain Pathol     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  463-7     Citation Subset:  IM    
Affiliation:
Department of Medical Genetics, University of Groningen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Amino Acid Substitution
Astrocytoma / genetics*
Child
Child, Preschool
DNA Mutational Analysis
Electrophoresis, Polyacrylamide Gel
Exons
Homozygote
Humans
Infant
Infant, Newborn
Introns
Mutation
Neoplasm, Residual / genetics
Polymerase Chain Reaction
Polymorphism, Genetic
Tumor Suppressor Protein p53 / genetics*,  physiology
Chemical
Reg. No./Substance:
0/Tumor Suppressor Protein p53

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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