MGMT promoter methylation status testing to guide therapy for glioblastoma: Refining the approach based on emerging evidence and current challenges

Alireza Mansouri, Laureen D. Hachem, Sheila Mansouri, Farshad Nassiri, Normand J. Laperriere, Daniel Xia, Neal I. Lindeman, Patrick Y. Wen, Arnab Chakravarti, Minesh P. Mehta, Monika E. Hegi, Roger Stupp, Kenneth D. Aldape, Gelareh Zadeh

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Glioblastoma (GBM) is the most common primary malignant brain tumor, with a universally poor prognosis. The emergence of molecular biomarkers has had a significant impact on histological typing and diagnosis, as well as predicting patient survival and response to treatment. The methylation status of the O 6-methylguanine-DNA methyl-transferase (MGMT) gene promoter is one such molecular biomarker. Despite the strong evidence supporting the role of MGMT methylation status in prognostication, its routine implementation in clinical practice has been challenging. The methods and optimal cutoff definitions for MGMT status determination remain controversial. Variation in detection methods between laboratories presents a major challenge for consensus. Moreover, consideration of other clinical and genetic/epigenetic factors must also be incorporated into treatment decision making. In this review, we distill the available evidence to summarize our position on the optimal use of available assays, and propose strategies for resolving cases with equivocal methylation status and a framework for incorporating this important assay into research and clinical practice.

Original languageEnglish (US)
Pages (from-to)167-178
Number of pages12
JournalNeuro-oncology
Volume21
Issue number2
DOIs
StatePublished - Feb 14 2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

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