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MGMT promoter methylation as a molecular biomarker in neuro-oncology: current practices, challenges, and future
Truman J Do1, Shameel Shafqat2, Sani H Kizilbash3
1Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, SW Rochester, Rochester, MN, 55905, USA.
Purpose:
MGMT promoter methylation (MGMTpm) is a well-established molecular biomarker in neuro-oncology. We review current practices, challenges, and future directions for MGMTpm as a biomarker in central nervous system (CNS) tumors.
Methods:
The literature on MGMT function, and MGMTpm clinical significance and testing in CNS tumors was reviewed.
Results:
We discuss the biological role of MGMT in DNA repair and the mechanisms by which MGMTpm leads to increased tumor sensitivity to alkylating agents. We summarize the clinical significance of MGMTpm in glioblastoma and its emerging relevance in other CNS tumors. Testing practices using methylation-specific PCR, pyrosequencing, and genome-wide methylation array-based approaches are discussed, along with challenges related to testing variability and "gray-zone" methylation, and emerging technologies such as nanopore sequencing.
Conclusions:
Despite ongoing technical and interpretative challenges, MGMTpm remains a robust and clinically valuable biomarker in neuro-oncology.
