Transcriptional diversity of long-term glioblastoma survivors Journal Article


Authors: Gerber, N. K.; Goenka, A.; Turcan, S.; Reyngold, M.; Makarov, V.; Kannan, K.; Beal, K.; Omuro, A.; Yamada, Y.; Gutin, P.; Brennan, C. W.; Huse, J. T.; Chan, T. A.
Article Title: Transcriptional diversity of long-term glioblastoma survivors
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.
Keywords: gene expression; glioblastoma; tcga; prognostic genes
Journal Title: Neuro-Oncology
Volume: 16
Issue: 9
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2014-09-01
Start Page: 1186
End Page: 1195
Language: English
DOI: 10.1093/neuonc/nou043
PROVIDER: scopus
PMCID: PMC4136896
PUBMED: 24662514
DOI/URL:
Notes: Export Date: 1 October 2014 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Timothy Chan
    317 Chan
  2. Yoshiya Yamada
    479 Yamada
  3. Philip H Gutin
    163 Gutin
  4. Cameron Brennan
    226 Brennan
  5. Antonio Marcilio Padula Omuro
    204 Omuro
  6. Kathryn Beal
    221 Beal
  7. Naamit Kurshan Gerber
    19 Gerber
  8. Anuj Goenka
    18 Goenka
  9. Marsha Reyngold
    104 Reyngold
  10. Jason T Huse
    143 Huse
  11. Sevin Turcan
    25 Turcan
  12. Kasthuri Srinivasan Kannan
    11 Kannan
  13. Vladimir Makarov
    57 Makarov