We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Pyrosequencing Analysis of O-6-Methylguanine-DNA Methyltransferase Methylation at Different Cut-Offs of Positivity Associated with Treatment Response and Disease-Specific Survival in Isocitrate Dehydrogenase-Wildtype Grade 4 Glioblastoma.
- Authors
Silva, Fábio França Vieira e; Di Domenico, Marina; Caponio, Vito Carlo Alberto; Pérez-Sayáns, Mario; Camolesi, Gisela Cristina Vianna; Rojo-Álvarez, Laura Isabel; Ballini, Andrea; García-García, Abel; Padín-Iruegas, María Elena; Suaréz-Peñaranda, Jose Manuel
- Abstract
The O-6-methylguanine-DNA methyltransferase (MGMT) gene is a critical guardian of genomic integrity. MGMT methylation in diffuse gliomas serves as an important determinant of patients' prognostic outcomes, more specifically in glioblastomas (GBMs). In GBMs, the absence of MGMT methylation, known as MGMT promoter unmethylation, often translates into a more challenging clinical scenario, tending to present resistance to chemotherapy and a worse prognosis. A pyrosequencing (PSQ) technique was used to analyze MGMT methylation status at different cut-offs (5%, 9%, and 11%) in a sample of 78 patients diagnosed with IDH-wildtype grade 4 GBM. A retrospective analysis was provided to collect clinicopathological and prognostic data. A statistical analysis was used to establish an association between methylation status and treatment response (TR) and disease-specific survival (DSS). The patients with methylated MGMT status experienced progressive disease rates of 84.6%, 80%, and 78.4% at the respective cut-offs of 5%, 9%, and 11%. The number was considerably higher when considering unmethylated patients, as all patients (100%), regardless of the cut-off, presented progressive disease. Regarding disease-specific survival (DSS), the Hazard Ratio (HR) was HR = 0.74 (0.45–1.24; p = 0.251); HR = 0.82 (0.51–1.33; p = 0.425); and HR = 0.79 (0.49–1.29; p = 0.350), respectively. Our study concludes that there is an association between MGMT unmethylation and worse TR and DSS. The 9% cut-off demonstrated a greater potential for patient survival as a function of time, which may shed light on the future need for standardization of MGMT methylation positivity parameters in PSQ.
- Subjects
O6-Methylguanine-DNA Methyltransferase; PYROSEQUENCING; METHYLATION; GLIOBLASTOMA multiforme; OVERALL survival
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 1, p612
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25010612