Methylation of p14 gene in meningiomas and its correlation to the p53 expression and mutation

Abstract

We have previously reported the statistically significant correlation of immunohistochemical expression of MIB-1 and p53 proteins among benign, atypical, and anaplastic meningiomas and p53 protein expression was high in atypical and anaplastic meningiomas. In the present study, we analyzed 22 cases of meningiomas for mutation of p53 gene in its spectrum of exon 5 to 8 using automated genetic analyzer. We did not find any mutation of p53 in any of these cases, thus suggesting the p53 protein expression is wild type. We analyzed 72 cases of meningiomas for determining the methylation status of p14 ARF gene and the immunohistochemical expression of MDM2 protein to explain p53 protein expression in these meningiomas. We found methylation of p14 ARF gene in five of 58 cases of benign meningiomas (8.6%), two of 10 cases of atypical meningiomas (20%), and two of four cases of anaplastic meningiomas (50%). In absence of p53 gene mutation, the high percentage of p14 ARF gene methylation in high-grade meningioma may have been responsible for accumulation of wild-type p53 protein. In addition, we also found the loss of MDM2 protein in high-grade meningiomas. These deregulations of p14-MDM2-p53 pathway may contribute to the malignant progression of meningioma.

Expression of Minichromosome Maintenance MCM6 Protein in Meningiomas is Strongly Correlated With Histologic Grade and Clinical Outcome

“…33 TP53 mutations or deletions were reported in atypical and anaplastic meningiomas, with a frequency ranging from 0% to 62%; however, grade I meningioma was not affected. 4,10,27,52,55 Nevertheless, there is considerable variability among the different studies. Amatya et al 4 did not find any mutation of TP53, despite a high frequency of p53 protein expression, thus suggesting that p53 protein is wild type.…”

Polymorphisms and DNA methylation of gene TP53 associated with extra-axial brain tumors

“…Agirre et al (2003) observed TP53 methylation in 8 of 25 cases (32%) of acute lymphoblastic leukemia. Amatya et al (2004) showed that TP53 methylation is frequent in low-grade gliomas; they observed that 60% of low-grade astrocytomas, 61% of oligoastrocytomas and 73% of oligodendrogliomas were methylated. The present study shows that the methylation of the TP53 gene is an important event associated with extra-axial brain tumors, since 37.5% of meningiomas, 30% of schwannomas and 52.6% of metastases were found to be hypermethylated, and TP53 methylation can be involved in the progression of these tumors, since we observed that 48% of the malignant tumors were methylated.…”

Wip1 over‐expression correlated with TP53/p14ARF pathway disruption in human astrocytomas

“…ARF plays a major role in the TP53 tumor suppressor pathway by antagonizing MDM2-mediated degradation of TP53, and mutations within each tumor affect only a single member of pathway in a mutually exclusive manner [20], p14 ARF loss of function should theoretically reduce the frequency of concomitant TP53 mutations [21]. In our study, however, we found no significant correlation between the p14 ARF inactivation and TP53 mutations; these seemed to be two unrelated events in astrocytomas.…”