Activation of PI3K/mTOR Pathway Occurs in Most Adult Low-Grade Gliomas and Predicts Patient Survival

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Activation of PI3K/mTOR Pathway Occurs in Most Adult Low-Grade Gliomas and Predicts Patient Survival

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dc.contributor.author Perez, Daniel A.
dc.contributor.author Polley, Mei-Yin
dc.contributor.author Vandenberg, Scott R.
dc.contributor.author Zheng, Shichun
dc.contributor.author Lamborn, Kathleen R.
dc.contributor.author Wiencke, John K.
dc.contributor.author Chang, Susan M.
dc.contributor.author Prados, Michael D.
dc.contributor.author Berger, Mitchel S.
dc.contributor.author Stokoe, David
dc.contributor.author Haas-Kogan, Daphne A.
dc.contributor.author McBride, Sean Matthew
dc.contributor.author Smith, Justin S.
dc.date.accessioned 2011-04-28T23:52:29Z
dc.date.issued 2009
dc.identifier.citation McBride, 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.issn 0167-594X en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4879187
dc.description.abstract Recent 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.iso en_US en_US
dc.publisher Springer US en_US
dc.relation.isversionof doi:10.1007/s11060-009-0004-4 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814032/pdf/ en_US
dash.license LAA
dc.subject low grade glioma en_US
dc.subject mTOR en_US
dc.subject rapamycin en_US
dc.subject PTEN en_US
dc.subject PRAS4 en_US
dc.title Activation of PI3K/mTOR Pathway Occurs in Most Adult Low-Grade Gliomas and Predicts Patient Survival en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Journal of Neuro-Oncology en_US
dash.depositing.author McBride, Sean Matthew
dc.date.available 2011-04-28T23:52:29Z
dash.affiliation.other HMS^Radiation Oncology-BWH-DFCI-CH en_US

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