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Journal of Neuro-Oncology

, Volume 137, Issue 2, pp 233–240 | Cite as

Temporal stability of MGMT promoter methylation in glioblastoma patients undergoing STUPP protocol

  • C. J. O’Regan
  • H. Kearney
  • A. Beausang
  • M. A. Farrell
  • F. M. Brett
  • J. B. Cryan
  • T. E. Loftus
  • P. G. Buckley
Laboratory Investigation

Abstract

Epigenetic silencing of O-6-methylguanine-DNA methyltransferase (MGMT) promoter via methylation in a glioblastoma (GBM), has been correlated with a more favourable response to alkylating chemotherapeutic agents such as temozolomide. The use of global methylation surrogates such as Long Interspersed Nucleotide Element 1 (LINE1) may also be valuable in order to fully understand these highly heterogeneous tumours. In this study, we analysed both original and recurrent GBMs in 22 patients (i.e. 44 tumours), for both MGMT and LINE1 methylation status. In the 22 patients: 14 (63.6%) displayed MGMT methylation stability in the recurrent GBM versus 8 (36.4%), with instability of methylation status. No significant differences in overall and progression free survival was evident between these two groups. LINE1 methylation status remained stable for 12 (54.5%) of recurrent GBM patients versus 9 (41%) of the patients with instability in LINE1 methylation status (p = 0.02), resulting in an increase in overall survival of the stable LINE1 group (p = 0.04). The results obtained demonstrated major epigenetic instability of GBMs treated with temozolomide as part of the STUPP protocol. GBMs appear to undergo selective evolution post-treatment, and have the ability to recur with a newly reprogrammed epigenetic status. Selective targeting of the altered epigenomes in recurrent GBMs may facilitate the future development of both prognostic biomarkers and enhanced therapeutic strategies.

Keywords

Glioblastoma MGMT Temzolamide Methylation Epigenetics 

Notes

Compliance with ethical standards

Conflict of interest

None of the authors have any conflict of interest in relation to this work.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • C. J. O’Regan
    • 1
  • H. Kearney
    • 2
  • A. Beausang
    • 2
  • M. A. Farrell
    • 2
  • F. M. Brett
    • 2
  • J. B. Cryan
    • 2
  • T. E. Loftus
    • 1
  • P. G. Buckley
    • 3
  1. 1.Department of Molecular PathologyBeaumont HospitalDublinIreland
  2. 2.Department of NeuropathologyBeaumont HospitalDublinIreland
  3. 3.Genomics Medicine IrelandDublinIreland

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