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ABSTRACT: Purpose
Understanding the molecular landscape of glioblastoma (GBM) is increasingly important in the age of targeted therapy. O-6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation and EGFR amplification are markers that may play a role in prognostication, treatment, and/or clinical trial eligibility. Quantification of MGMT and EGFR protein expression may offer an alternative strategy towards understanding GBM. Here, we quantify baseline expression of MGMT and EGFR protein in newly diagnosed GBM samples using mass spectrometry. We correlate findings with MGMT methylation and EGFR amplification statuses and survival.Methods
We retrospectively identified adult patients with newly diagnosed resected GBM. MGMT and EGFR protein expression were quantified using a selected reaction monitoring mass spectrometry assay. Protein levels were correlated with MGMT methylation and EGFR amplification and survival data.Results
We found a statistically significant association between MGMT protein expression and promoter methylation status (p?=?0.02) as well as between EGFR protein expression and EGFR amplification (p?ConclusionsUnlike EGFR protein expression and EGFR amplification which are strongly associated, only a weak association was seen between MGMT protein expression and promoter methylation. Quantification of MGMT protein expression was inferior to MGMT methylation for prognostication in GBM. Discordance was observed between EGFR amplification and EGFR protein expression; additional study is warranted to determine whether EGFR protein expression is a better biomarker than EGFR amplification for clinical decisions and trial enrollment.
SUBMITTER: Schaff LR
PROVIDER: S-EPMC6939885 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Schaff Lauren R LR Yan Dongyao D Thyparambil Sheeno S Tian Yuan Y Cecchi Fabiola F Rosenblum Marc M Reiner Anne S AS Panageas Katherine S KS Hembrough Todd T Lin Andrew L AL
Journal of neuro-oncology 20191210 1
<h4>Purpose</h4>Understanding the molecular landscape of glioblastoma (GBM) is increasingly important in the age of targeted therapy. O-6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation and EGFR amplification are markers that may play a role in prognostication, treatment, and/or clinical trial eligibility. Quantification of MGMT and EGFR protein expression may offer an alternative strategy towards understanding GBM. Here, we quantify baseline expression of MGMT and EGFR protein i ...[more]