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

Laura Dovek, Nhung T. Nguyen, Byram H. Ozer, Ning Li, Robert M. Elashoff, Richard M. Green, Linda Liau, P. Leia Nghiemphu, Timothy F. Cloughesy, Albert Lai

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
Pages (from-to)194-202
Number of pages9
JournalNeuro-Oncology Practice
Volume6
Issue number3
DOIs
StatePublished - Jun 1 2019
Externally publishedYes

Keywords

  • Glioblastoma
  • Glioma
  • MGMT
  • Promoter methylation
  • Temozolomide

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Fingerprint Dive into the research topics of 'Correlation of commercially available quantitative MGMT (O-6-methylguanine-DNA methyltransferase) promoter methylation scores and GBM patient survival'. Together they form a unique fingerprint.

  • Cite this

    Dovek, L., Nguyen, N. T., Ozer, B. H., Li, N., Elashoff, R. M., Green, R. M., Liau, L., Leia Nghiemphu, P., Cloughesy, T. F., & Lai, A. (2019). Correlation of commercially available quantitative MGMT (O-6-methylguanine-DNA methyltransferase) promoter methylation scores and GBM patient survival. Neuro-Oncology Practice, 6(3), 194-202. https://doi.org/10.1093/nop/npy028