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

Neuro-oncology Practice
Laura DovekAlbert Lai

Abstract

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. 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). 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, wh...Continue Reading

References

Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Mar 17, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrick Y WenSusan M Chang
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Feb 21, 2014·The New England Journal of Medicine·Mark R GilbertMinesh P Mehta
Feb 21, 2014·The New England Journal of Medicine·Olivier L ChinotTimothy Cloughesy

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