Figure 1. MGMT promoter CpG sites covered by TRUPCR™ MGMT Assay

The MGMT (O6-methylguanine-DNA methyltransferase) gene, located on chromosome 10q26, plays a critical role in DNA repair by removing alkyl groups from the O6 position of guanine. Silencing of this gene through promoter methylation is a key epigenetic event in various cancers, particularly glioblastomas, and is associated with improved response to alkylating agents like temozolomide.

The MGMT promoter is rich in CpG islands—stretches of CG-rich DNA (300–3000 bp) where methylation occurs. This modification, catalyzed by DNA methyltransferases, leads to epigenetic silencing of the gene. Among the 98 CpG sites in the promoter region, methylation within two specific clusters—DMR1 (CpGs 25–50) and DMR2 (CpGs 73–90)—has shown the strongest correlation with transcriptional silencing.

The TRUPCR™ MGMT Assay offers precise detection of methylation at five critical CpG sites (79, 80, 81, 82, and 83) located within DMR2, a hotspot for epigenetic regulation (Figure 1). These sites start at chr10:131265536 (hg19 build) and have been widely reported as clinically relevant for determining MGMT silencing status.

By using a real-time PCR–based approach, the TRUPCR™ MGMT Assay provides a sensitive, rapid, and reliable method for assessing MGMT methylation, supporting personalized treatment decisions in oncology.