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- W2767454901 abstract "Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer. One of the most robust clinically-obtained biomarkers available for GBM is MGMT promoter methylation, which predicts improved outcome to standard of care alkylating chemotherapy. MGMT promoter leads to gene silencing of MGMT resulting in reduced DNA repair activity. Current commercial MGMT testing-such as available through LabCorp-use quantitative methylation-specific-PCR with a single threshold value to distinguish methylated from unmethylated MGMT tumors. In this study, we sought to determine whether the magnitude of MGMT methylation as determined by LabCorp testing correlates with outcome in our GBM patients. We identified 243 newly-diagnosed GBM patients with LabCorp-derived MGMT scores performed on pre-treatment tissue samples. In addition, we further required that patients’ samples were IDH1 wild-type and were treated with temozolomide. This resulted in a cohort of 202 patients that were eligible for inclusion in this study. We used both Kaplan-Meier and multivariate analysis of overall survival to determine whether unmethylated and methylated groups could be further stratified. First, we validated that the standard LabCorp threshold of 2 could separate our cohort by survival. We then sub-stratified the <2 (unmethylated) group and found that patients with scores 3 0.1 had higher survival than those with methylation scores < 0.1. Lastly, when we sub-stratified the 3 2 (methylated) group, we found that patient with scores 3 30 trended towards improved survival. In our large single institution cohort, our results suggest the use of 4 (instead of 2) clinically-relevant methylation categories in which unmethylated can be subdivided into unmethylated and partially methylated groups and methylated can be subdivided into methylated and super-methylated groups. Our results suggest a ‘dose-dependent’ relationship of quantitative MGMT methylation to outcome that is obscured by current binary stratification." @default.
- W2767454901 created "2017-11-17" @default.
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- W2767454901 date "2017-11-01" @default.
- W2767454901 modified "2023-09-28" @default.
- W2767454901 title "PATH-17. CORRELATION OF COMMERCIALLY-AVAILABLE QUANTITATIVE MGMT (O-6-METHYLGUANINE-DNA METHYLTRANSFERASE) METHYLATION SCORES AND OVERALL GBM PATIENT SURVIVAL" @default.
- W2767454901 doi "https://doi.org/10.1093/neuonc/nox168.708" @default.
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