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Neuro Oncol. 2014 Sep;16(9):1186-95. doi: 10.1093/neuonc/nou043. Epub 2014 Mar 23.

Transcriptional diversity of long-term glioblastoma survivors.

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  • 1Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (N.K.G., A.G., M.R., K.B., Y.Y., T.A.C.); Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (S.T., V.M., K.K., T.A.C.); Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (A.O.); Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New York (P.G., C.W.B.); Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (J.T.H.).

Abstract

BACKGROUND:

Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTSs) may provide important insight into the biology of GBM.

METHODS:

We identified 7 patients with GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival >48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository for Molecular Brain Neoplasia Data [REMBRANDT]) and analyzed the transcriptomal characteristics of these LTSs.

RESULTS:

The median overall survival of our cohort was 62.5 months. LTSs were distributed between the proneural (n = 2), neural (n = 2), classical (n = 2), and mesenchymal (n = 1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identities. The majority of the MSKCC LTSs (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutation, and IDH mutation occurred in a minority of the TCGA LTSs as well. A set of 60 genes was found to be differentially expressed in the MSKCC and TCGA LTSs.

CONCLUSIONS:

While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression.

© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

KEYWORDS:

TCGA; gene expression; glioblastoma; prognostic genes

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