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NDRG1 prognosticates the natural course of disease in WHO grade II glioma


Blaes, J; Weiler, M; Sahm, F; Hentschel, B; Osswald, M; Czabanka, M; Thomé, C M; Schliesser, M G; Pusch, S; Luger, S; Winkler, F; Radbruch, A; Jugold, M; Simon, M; Steinbach, J P; Schackert, G; Tatagiba, M; Westphal, M; Tonn, J C; Gramatzki, D; Pietsch, T; Hartmann, C; Glimm, H; Vajkoczy, P; von Deimling, A; Platten, M; Weller, M; Wick, W (2014). NDRG1 prognosticates the natural course of disease in WHO grade II glioma. Journal of Neuro-Oncology, 117(1):25-32.

Abstract

There is a lack of relevant prognostic and predictive factors in neurooncology besides mutation of isocitrate dehydrogenase 1, codeletion of 1p/19q and promoter hypermethylation of O (6) -methylguanine-DNA-methyltransferase. More importantly, there is limited translation of these factors into clinical practice. The cancer genome atlas data and also clinical correlative analyses suggest a pivotal role for the epidermal growth factor receptor /protein kinase B/mammalian target of rapamycin (mTOR) pathway in both biology and the clinical course of gliomas. However, attempts to stratify gliomas by activating alterations in this pathway have failed thus far. The tumors of 40 patients with WHO grade II gliomas without immediate postoperative genotoxic treatment and known progression and survival status at a median follow-up of 12.2 years were analyzed for expression of the mTOR complex 2 downstream target N-myc downstream regulated gene (NDRG)1 using immunohistochemistry. Baseline characteristics for NDRG1 absent/low versus moderate/high patients were similar. Time to reintervention was significantly longer in the NDRG1 group (P = 0.026). NDRG1 may become a novel biomarker to guide the decision which WHO°II glioma patients may be followed without postsurgical intervention and which patients should receive genotoxic treatment early on. Validation of this hypothesis will be possible with the observational arm of the RTOG 9802 and the pretreatment step of the EORTC 22033/26032 trials.

There is a lack of relevant prognostic and predictive factors in neurooncology besides mutation of isocitrate dehydrogenase 1, codeletion of 1p/19q and promoter hypermethylation of O (6) -methylguanine-DNA-methyltransferase. More importantly, there is limited translation of these factors into clinical practice. The cancer genome atlas data and also clinical correlative analyses suggest a pivotal role for the epidermal growth factor receptor /protein kinase B/mammalian target of rapamycin (mTOR) pathway in both biology and the clinical course of gliomas. However, attempts to stratify gliomas by activating alterations in this pathway have failed thus far. The tumors of 40 patients with WHO grade II gliomas without immediate postoperative genotoxic treatment and known progression and survival status at a median follow-up of 12.2 years were analyzed for expression of the mTOR complex 2 downstream target N-myc downstream regulated gene (NDRG)1 using immunohistochemistry. Baseline characteristics for NDRG1 absent/low versus moderate/high patients were similar. Time to reintervention was significantly longer in the NDRG1 group (P = 0.026). NDRG1 may become a novel biomarker to guide the decision which WHO°II glioma patients may be followed without postsurgical intervention and which patients should receive genotoxic treatment early on. Validation of this hypothesis will be possible with the observational arm of the RTOG 9802 and the pretreatment step of the EORTC 22033/26032 trials.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2014
Deposited On:13 Aug 2014 14:18
Last Modified:05 Apr 2016 17:50
Publisher:Springer
ISSN:0167-594X
Additional Information:The final publication is available at link.springer.com
Publisher DOI:https://doi.org/10.1007/s11060-013-1357-2
PubMed ID:24395351
Permanent URL: https://doi.org/10.5167/uzh-95403

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