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Identifying the optimal cutoff point for MGMT promoter methylation status in glioblastoma

Ngan Nguyen, Jordan Redfield, Matthew T. Ballo, Madison Michael, Jeffrey Sorenson, Daniel T. Dibaba, Jim Y. Wan, Glenda Maria Delgado Ramos, Manjari Pandey

2021CNS Oncology19 citationsDOIOpen Access PDF

Abstract

Aim: To define the optimal cutoff point for determining methylation status of O6-methylguanine-DNA methyltransferase (MGMT) by pyrosequencing in glioblastoma. Patients & methods: A retrospective study of 109 glioblastoma patients was performed to determine the optimal cutoff point for MGMT methylation status. Results: Receiver operating characteristic (ROC) analysis revealed 21% as the optimal cutoff (sensitivity: 68%; specificity: 59%) for MGMT methylation corresponding with the highest likelihood ratio of 1.66 and accuracy of 0.65. Methylation status (hazard ratio: 0.453; 95% CI: 0.279–0.735; p = 0.001) was associated with better overall survival. The crude model indicated linearity between methylation percent and survival rate; an increase of 10% of methylation resulted in a reduction of risk of death by 20% (p = 0.004). Conclusion: ROC analysis determined 21% as the optimal cutoff point for MGMT methylation status by pyrosequencing.

Topics & Concepts

MethylationCutoffReceiver operating characteristicMedicineOncologyDNA methylationHazard ratioMethyltransferaseGlioblastomaInternal medicineCancer researchBiologyConfidence intervalGeneGeneticsGene expressionQuantum mechanicsPhysicsGlioma Diagnosis and TreatmentBrain Metastases and TreatmentEpigenetics and DNA Methylation
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