Correlation of the quantitative level of MGMT promoter methylation and overall survival in primary diagnosed glioblastomas using the quantitative MethyQESD method

Abstract

<jats:sec><jats:title>Aims</jats:title><jats:p><jats:italic>O</jats:italic>(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is a high predictive factor for therapy results of temozolomide in patients with glioma. The objective of this work was to analyse the impact of MGMT promoter methylation in patients with primary diagnosed glioblastoma (GBM) relating to survival using a quantitative method (methylation quantification of endonuclease-resistant DNA, MethyQESD) by verifying a cut-off point for MGMT methylation provided by the literature (&lt;/≥10%) and calculating an optimal cut-off.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>67 patients aged 70 years or younger, operated between January 2013 and December 2015, with newly diagnosed IDH wild-type GBM and clinical follow-up were retrospectively investigated in this study. A known MGMT promoter methylation status was the inclusion criteria.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Median overall survival (OS) was 16.9 months. Patients who had a methylated MGMT promoter region of ≥10% had an improved OS compared with patients with a methylated promoter region of &lt;10% (p=0.002). Optimal cut-off point for MGMT promoter methylation was 11.7% (p=0.012).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The results confirm that the quantitative level of MGMT promoter methylation is a positive prognostic factor in newly diagnosed patients with GBM. The cut-off provided by the literature (&lt;/≥10%) and the calculated optimal cut-off value of 11.7% give a statistically significant separation. Hence, MethyQESD is a reliable method to calculate MGMT promoter methylation in GBM.</jats:p></jats:sec>

MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial

“…The role of MGMT promoter methylation for therapy response has been reported previously, especially for glioblastoma. In glioblastoma, an increased MGMT promoter methylation has a predictive impact for increased pCR and therapy response to temozolomide [19,20].…”

“…Results for glioblastoma were determined via MethyQESD method, described by Bettstetter et al [28], using MGMT promoter methylation specific quantitative real-time PCR [20]. Bettstetter et al performed a proof-of-principle, using survival data for cutoff-fitting.…”

“…If more than 11.7% of MGMT gene promoter were methylated, the tumor was determined as MGMT promoter hypermethylated [28]. In our methylation assay, we used the common cutoff of 10 percent, determined via different methylation assays as previously described [20].…”

“…For glioblastoma multiforme, it has been shown that tumors with no or low levels of MGMT activity are more responsive to therapy with the alkylating drug temozolomide [19,20]. MGMT inactivation by epigenetic silencing through methylation of CpG islands in the promoter region correlates with the sensitivity of tumor cells to alkylating agents.…”

Age-Adjusted Charlson Comorbidity Index in Recurrent Glioblastoma: A New Prognostic Factor?

“…In patients with inoperable tumor recurrence, a biopsy was performed for histopathological diagnosis. Within the rst surgery, molecular pathological ndings were analyzed according to the WHO criteria of 2016 [21] (i.e., O-6methylguanine-DNA-methyltransferase [MGMT] promotor methylation [22], mutation status of isocitrate dehydrogenase [IDH] [21]). In the case of recurrence, no further investigations were made.…”