TP53 mutations in human meningiomas.
Overexpression of p53 has been reported to play a role in the development of neoplasms of the central nervous system. Meningiomas are generally benign intracranial tumors originating from the meninges. Overexpression of the p53 protein in meningiomas and an association with histological type and recurrence has been reported. Mutation of the TP53 gene leads to a more stable p53 protein in quantities high enough for detection by immunohistochemistry. In the search for these mutations the core domain of the TP53 gene of meningiomas has been analyzed. Only a very low incidence of mutations was reported. The apparent discordance between overexpression of p53 protein and TP53 gene mutations may be explained by mutations located outside the core domain. This issue was addressed in the present study. All 11 exons of 17 meningiomas were analyzed for DNA alterations by PCR single-strand conformation polymorphism (PCR-SSCP) analysis with subsequent sequencing. PCR-SSCP analysis showed a various number of band shifts and nucleotide alterations, caused either by alterations in the flanking introns or common polymorphisms (codon 36 and 72). The allele frequencies of the polymorphisms found in this small population of tumors resemble the frequencies reported in the literature. In addition, three nucleotide changes located in introns 2, 3 and 7 were found in 11, 3 and 4, respectively, of 17 specimens. Based on this study and on reports by others we conclude that it is not very likely that TP53 mutations are involved in the etiology of meningiomas.
Verheijen
F M
FM
Department of Endocrinology, University Medical Center Utrecht, The Netherlands. f.verheijen@twenteborg.nl
Sprong
M
M
Kloosterman
J M E
JM
Blaauw
G
G
Thijssen
J H H
JH
Blankenstein
M A
MA
D000328:Adult; D000368:Aged; D003062:Codon; D005091:Exons; D005260:Female; D016158:Genes, p53; D006801:Humans; D008297:Male; D008579:Meningioma / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA
D003062:Codon