title: A role for the p53 pathway in the pathology of meningiomas with NF2 loss.
abstract: 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.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: ZeNan
authors.initials: Z
authors.lastname: Chang
authors.forename: Chin-Lin
authors.initials: CL
authors.lastname: Guo
authors.forename: Iris
authors.initials: I
authors.lastname: Ahronowitz
authors.forename: Anat O
authors.initials: AO
authors.lastname: Stemmer-Rachamimov
authors.forename: Mia
authors.initials: M
authors.lastname: MacCollin
authors.forename: Fabio P
authors.initials: FP
authors.lastname: Nunes
mesh_terms: D000368:Aged; D001120:Arginine / Q000235:genetics; D015331:Cohort Studies; D016001:Confidence Intervals; D004252:DNA Mutational Analysis / Q000379:methods; D018450:Disease Progression; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008577:Meningeal Neoplasms / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008579:Meningioma / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D016518:Neurofibromatosis 2 / Q000150:complications / Q000235:genetics / Q000473:pathology*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics; D011392:Proline / Q000235:genetics; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53; D001120:Arginine; D011392:Proline