Methylation of p14(ARF) gene in meningiomas and its correlation to the p53 expression and mutation.
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.
Amatya
Vishwa Jeet
VJ
Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. vjamatya@mac.com
Takeshima
Yukio
Y
Inai
Kouki
K
D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008579:Meningioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051736:Proto-Oncogene Proteins c-mdm2; D025803:Tumor Suppressor Protein p14ARF / Q000032:analysis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2