Correlation of commercially available quantitative MGMT (O-6-methylguanine-DNA methyltransferase) promoter methylation scores and GBM patient survival.

Content Provider	Europe PMC
Author	Dovek, Laura Nguyen, Nhung T Ozer, Byram H Li, Ning Elashoff, Robert M Green, Richard M Liau, Linda Nghiemphu, P Leia Cloughesy, Timothy F Lai, Albert
Copyright Year	2018
Abstract	Abstract Background Between 2011 and 2016, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation testing at University of California Los Angeles (UCLA) was performed through LabCorp, using a threshold of 2 to distinguish MGMT methylated from unmethylated tumors. In this study, we sought to determine whether the magnitude of the methylation score correlated with outcome. Methods We identified 165 newly diagnosed glioblastoma (GBM) isocitrate dehydrogenase (IDH) wild-type and temozolomide-treated upfront patients at UCLA and Kaiser Permanente Los Angeles with LabCorp-derived quantitative MGMT scores obtained on pretreatment tissue samples. Using LabCorp’s threshold, we found 102 unmethylated and 63 methylated patients. We then further substratified each group based on the magnitude of the score, and performed Kaplan-Meier and Cox regression analyses of overall survival (OS) and progression-free survival (PFS). Results We validated that the standard LabCorp threshold of 2 could separate our cohort by survival, showing longer OS and PFS for MGMT methylated patients vs unmethylated patients. Cox regression analysis confirmed that MGMT (<1) patients had worse outcome, with OS and PFS hazard ratios of 2.375 (P = .053) and 2.463 (P = .023), respectively, when compared to the MGMT (1-1.99) patients. Contrary to our expectation, when we substratified the ≥2 (methylated) group, we did not find a dose-dependent relationship between the magnitude of MGMT methylation and improved survival. Conclusions The MGMT unmethylated group contains a partially methylated group (greater than 1) that shares survival benefits similar to the methylated group. However, we did not demonstrate an association of very high methylation scores with increased survival. These findings will require validation in additional independent clinical data sets.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6656311&blobtype=pdf
Page Count	9
ISSN	20542577
Volume Number	6
DOI	10.1093/nop/npy028
PubMed Central reference number	PMC6656311
Issue Number	3
PubMed reference number	31386024
Journal	Neuro-Oncology Practice [Neurooncol Pract]
e-ISSN	20542585
Language	English
Publisher	Oxford University Press
Publisher Date	2018-08-08
Publisher Place	US
Access Restriction	Open
Rights License	This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Subject Keyword	glioma glioblastoma MGMT promoter methylation temozolomide
Content Type	Text
Resource Type	Article
Subject	Neurology Medicine Oncology