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61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

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Expression changes of TP53-regulator PPM1D and Reprimo in atypical and anaplastic meningiomas

Meeting Abstract

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  • Shinjiro Fukami - The Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan
  • Hans-Jacob Steiger - Neurochirurgische Klinik, Heinrich-Heine Universität, Düsseldorf, Germany
  • Guido Reifenberger - Abteilung für Neuropathologie, Heinrich-Heine Universität, Germany
  • Markus J. Riemenschneider - Abteilung für Neuropathologie, Heinrich-Heine Universität, Germany

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP1733

doi: 10.3205/10dgnc204, urn:nbn:de:0183-10dgnc2046

Published: September 16, 2010

© 2010 Fukami et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Anaplastic meningiomas have a very sad prognosis with a median survival of under 2 years. Therefore, precise diagnosis and understanding of the biological behavior of anaplastic meningioma is very important. Nuclear immunoreactiviy of p53 protein has been detected in variable fractions of meningioma. However, in meningiomas, including atypical and malignant meningioma, p53 mutations are apparently rare. Therefore, there might be another regulating mechanism controlling p53 protein expression. Protein phosphatase 1D magnesium-dependent, delta isoform (PPM1D) and Reprimo (RPRM) are thought to be some of the regulators of the p53 protein. The aim of our paper is to clarify the expression level and regulation mechanism of PPM1D and PRRM in various grades of meningiomas.

Methods: Genomic DNA and mRNA were extracted from frozen-tissue sections of meningiomas (grade I 20cases, grade II 17cases, grade III 20cases). In these cases, we could obtain mRNA from some cases (grade I 18 cases, grade II 11cases, grade III 9 cases). For the analysis of mRNA expression and genomic gain of PPM1D, we performed semiquantative duplex RT-PCR, real-time RT-PCR and semiquantative duplex PCR. Using semiquantative duplex RT-PCR, we also analyzed several genes, which are located near PPM1D in genomic map of 17q22-23. For the analysis of mRNA expression of RPRM, we used real-time RT-PCR. In addition, we investigated the DNA methylation status of RPRM using sodium bisulfate sequencing.

Results: mRNA expression of PPM1D in grade II, III- meningiomas is statically significantly higher than in grade I meningiomas. In all other genes, which are located near PPM1D on the genomic map of 17q22-23, there was no statistical significance between grade I and grade II, III. Therefore PPM1D is the putative main amplification-target in 17q22-24 of atypical and anaplastic meningioma. Interestingly, values of PPM1D mRNA highly correlate with value of genomicDNA. On the other hand, for the mRNA expression of RPRM, there was no statistical significance between grade I and grade II, III. Among 9 anaplastic meningiomas, however, the expression of RPRM is highly suppressed in 4 cases. In addition, 35%( 7/20) cases of grade III meningiomas have highly methylated CpG on the translation site of RPRM. Correlation of mRNA expression between RPRM and PPM1D is not significant. However, in atypical and anaplastic cases, tumors, which express PPM1D highly, have a relatively suppressed RPRM expression.

Conclusions: PPM1D and RPRM may contribute to the development of malignant transformation in meningioma pathogenesis.