Expression and gene doses changes of the p53-regulator PPM1D in meningiomas: a role in meningioma progression?
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The aim of our study was to clarify the expression and gene copy number levels of protein phosphatase 1D magnesium-dependent, delta isoform (PPM1D), which is thought to be a regulator of the p53 protein in meningiomas of all three different WHO grades. Genomic DNA and mRNA were extracted from frozen tissues of meningiomas (WHO grade I, 20 cases; grade II, 17 cases; grade III, 20 cases). For analysis of the mRNA expression and gene dosage level of PPM1D, semiquantitative duplex RT-PCR, real-time RT-PCR, and semiquantitative duplex PCR were performed. We also analyzed several genes which locate near PPM1D in the genomic locus 17q22–24 using semiquantitative duplex RT-PCR. We found that the mean mRNA expression of PPM1D is higher in WHO grade II and III meningiomas than in grade I tumors. This finding is accompanied by moderate gene dosage increases for PPM1D in meningiomas of higher grades. Other genes located in the vicinity of PPM1D also showed mRNA overexpression in single meningioma cases. For these genes, however, no significant expression differences between meningioma grades could be observed. Thus, PPM1D in the chromosomal location 17q22–24 might be the most relevant candidate gene with respect to a potential functional implication in meningioma progression.
KeywordsAtypical and anaplastic meningioma Protein phosphatase 1D magnesium-dependent delta isoform (PPM1D) p53 Progression
The authors are indebted to Dr. Edward Barroga, Associate Professor and Senior Medical Editor from the Department of International Medical Communications of Tokyo Medical University for editing and reviewing the English manuscript. SF would like to thank Professor Haraoka (Department of Neurosurgery, Tokyo Medical University) and Professor Reifenberger (Department of Neuropathology, Heinrich-Heine University) for helpful suggestions in the initiation of the study.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest associated with this study.
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