TP53 Mutations in Human Meningiomas

Abstract

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.

Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression

“…Of 15 samples showing alterations, seven meningiomas had changes in codon 72. This is the same position that Verheijen et al (2002) described in their paper. The described Arg72Pro amino acid change at codon 72 (rs1042522) is a well-known single nucleotide polymorphism, which frequently occurs in various tumour sites including brain tumours such as glioblastoma (Faria et al 2012).…”

“…Exon 4 is a part of the core domain of p53, an important domain by which the protein binds to DNA. The reason for choosing this exon comes from the paper by Verheijen et al (2002) who found different migration patterns of exon 4 PCR-SSCP products in 10 of 17 investigated meningiomas. We found nucleotide alterations in 35.7% of meningiomas.…”

Specific Genes Expressed in Association with Progesterone Receptors in Meningioma

“…Analyses of genetic aberrations in meningioma also indicate that losses of chromosome 9p (which occur in approximately one third of cases and represent the third most frequently reported aberration in meningioma) are associated with loss of both wild-type copies of two genes associated with cell cycle control, CDKN2A (9p21) and CDKN2B (9p21), and that this change is associated with progression to anaplasia in meningiomas. Amplification of 17q has also been noted in anaplastic meningiomas; however, a clear association between this amplification and TP53 mutations has not yet been shown (35).…”

DNA Microarray Analysis Identifies CKS2 and LEPR as Potential Markers of Meningioma Recurrence

“…Recent data showed that gene expression of cyclin-dependent kinase subunit Cks2 is repressed by the tumor suppressor p53 [38]. Although p53 mutations are rare in meningiomas [39], several reports showed higher expression in atypical and anaplastic meningiomas [40,41] and in one set of data based on an analysis of 80 meningiomas, specifically in grade I relapsing meningiomas [42]. These observations support future investigations on the relationship between higher p53 and CKS2 expression levels in meningiomas that switch to aggressive patterns of growth.…”