title: Expression and gene doses changes of the p53-regulator PPM1D in meningiomas: a role in meningioma progression?
abstract: 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.
authors.affiliation: Department of Neurosurgery, Heinrich-Heine University, Düsseldorf, Germany. fukami-nsu@umin.ac.jp.|Department of Neurosurgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-023, Japan. fukami-nsu@umin.ac.jp.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Fukami
authors.affiliation: Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Riemenschneider
authors.affiliation: Department of Neurosurgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-023, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kohno
authors.affiliation: Department of Neurosurgery, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Hans Jakob
authors.initials: HJ
authors.lastname: Steiger
mesh_terms: D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D000071636:Protein Phosphatase 2C / Q000235:genetics* / Q000502:physiology; D012334:RNA, Neoplasm / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C000607458:PPM1D protein, human; D000071636:Protein Phosphatase 2C
keywords: Atypical and anaplastic meningioma; Progression; Protein phosphatase 1D magnesium-dependent delta isoform (PPM1D); p53