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A role for the p53 pathway in the pathology of meningiomas with NF2 loss

Chang, ZeNan and Guo, Chin-Lin and Ahronowitz, Iris and Stemmer-Rachamimov, Anat O. and MacCollin, Mia and Nunes, Fabio P. (2009) A role for the p53 pathway in the pathology of meningiomas with NF2 loss. Journal of Neuro-oncology, 91 (3). pp. 265-270. ISSN 1573-7373.

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The neurofibromatosis 2 locus (NF2) is inactivated through mutation and loss of heterozygosity (LOH) in 40–65% of all sporadic meningiomas, while the role of the p53 tumor suppression pathway in meningioma initiation and progression is still unclear. This study aims to determine if a p53 codon 72 arginine-to-proline polymorphism, found to be correlated with cancer development and cancer patient survival in other tumors, is associated with sporadic meningioma initiation or progression. We investigated Pro72 incidence in a cohort of 92 sporadic meningiomas and analyzed its association with histological grade (WHO classification) and with NF2 LOH (determined using polymorphic microsatellite markers on 22q). The Pro72 allele was not found to be selected for in the cohort. However, in the subgroup of meningiomas with NF2 LOH and carrying Pro72, 50.0% had high grade tumors (WHO grades II and III) compared to only 14.3% of those without NF2 LOH (OR = 6.0, CI = 1.56–23.11, P = 0.012). The significant association occurred only when considering subgroups of meningiomas with or without NF2 LOH, suggesting that not including NF2 status when analyzing study cohorts may explain the variability seen in the literature where all meningiomas were grouped together. Our data suggests a role for the p53 pathway in the progression of meningiomas in which NF2 is inactivated, and highlights the importance of accounting for NF2 LOH in future studies of meningiomas and the p53 pathway.

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Additional Information:© 2009 Springer. Received: 24 July 2008; accepted: 13 October 2008; published online: 1 November 2008. Funded by National Institutes of Health; Grant Number: 1 R01 NS40527 to MM. The authors would also like to thank all the patients who donated tissues for this study and to thank the Center for Excellence in Education for supporting ZC.
Funding AgencyGrant Number
NIH1 R01 NS40527
Center for Excellence in EducationUNSPECIFIED
Subject Keywords:NF2; Mdm2; p53; Pro72; Meningiomas
Issue or Number:3
Record Number:CaltechAUTHORS:20090430-152807688
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:14129
Deposited By: Jason Perez
Deposited On:13 Aug 2009 21:06
Last Modified:03 Oct 2019 00:47

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