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dc.contributor.authorPerez, Daniel A.
dc.contributor.authorPolley, Mei-Yin
dc.contributor.authorVandenberg, Scott R.
dc.contributor.authorZheng, Shichun
dc.contributor.authorLamborn, Kathleen R.
dc.contributor.authorWiencke, John K.
dc.contributor.authorChang, Susan M.
dc.contributor.authorPrados, Michael D.
dc.contributor.authorBerger, Mitchel S.
dc.contributor.authorStokoe, David
dc.contributor.authorHaas-Kogan, Daphne A.
dc.contributor.authorMcBride, Sean Matthew
dc.contributor.authorSmith, Justin S.
dc.date.accessioned2011-04-28T23:52:29Z
dc.date.issued2009
dc.identifier.citationMcBride, Sean M., Daniel A. Perez, Mei-Yin Polley, Scott R. Vandenberg, Justin S. Smith, Shichun Zheng, Kathleen R. Lamborn, et al. 2009. Activation of PI3K/mTOR pathway occurs in most adult low-grade gliomas and predicts patient survival. Journal of Neuro-Oncology 97(1): 33-40.en_US
dc.identifier.issn0167-594Xen_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4879187
dc.description.abstractRecent evidence suggests the Akt-mTOR pathway may play a role in development of low-grade gliomas (LGG). We sought to evaluate whether activation of this pathway correlates with survival in LGG by examining expression patterns of proteins within this pathway. Forty-five LGG tumor specimens from newly diagnosed patients were analyzed for methylation of the putative 5′-promoter region of PTEN using methylation-specific PCR as well as phosphorylation of S6 and PRAS40 and expression of PTEN protein using immunohistochemistry. Relationships between molecular markers and overall survival (OS) were assessed using Kaplan-Meier methods and exact log-rank test. Correlation between molecular markers was determined using the Mann-Whitney U and Spearman Rank Correlation tests. Eight of the 26 patients with methylated PTEN died, as compared to 1 of 19 without methylation. There was a trend towards statistical significance, with PTEN methylated patients having decreased survival (P = 0.128). Eight of 29 patients that expressed phospho-S6 died, whereas all 9 patients lacking p-S6 expression were alive at last follow-up. There was an inverse relationship between expression of phospho-S6 and survival (P = 0.029). There was a trend towards decreased survival in patients expressing phospho-PRAS40 (P = 0.077). Analyses of relationships between molecular markers demonstrated a statistically significant positive correlation between expression of p-S6(235) and p-PRAS40 (P = 0.04); expression of p-S6(240) correlated positively with PTEN methylation (P = 0.04) and negatively with PTEN expression (P = 0.03). Survival of LGG patients correlates with phosphorylation of S6 protein. This relationship supports the use of selective mTOR inhibitors in the treatment of low grade glioma.en_US
dc.language.isoen_USen_US
dc.publisherSpringer USen_US
dc.relation.isversionofdoi:10.1007/s11060-009-0004-4en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814032/pdf/en_US
dash.licenseLAA
dc.subjectlow grade gliomaen_US
dc.subjectmTORen_US
dc.subjectrapamycinen_US
dc.subjectPTENen_US
dc.subjectPRAS4en_US
dc.titleActivation of PI3K/mTOR Pathway Occurs in Most Adult Low-Grade Gliomas and Predicts Patient Survivalen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalJournal of Neuro-Oncologyen_US
dash.depositing.authorMcBride, Sean Matthew
dc.date.available2011-04-28T23:52:29Z
dash.affiliation.otherHMS^Radiation Oncology-BWH-DFCI-CHen_US
dc.identifier.doi10.1007/s11060-009-0004-4*
dash.authorsorderedfalse
dash.contributor.affiliatedMcBride, Sean


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