Schlosser, Sabrina and Wagner, Sabine and Muehlisch, Joerg and Hasselblatt, Martin and Gerss, Joachim and Wolff, Johannes E. A. and Fruehwald, Michael C. (2010) MGMT as a Potential Stratification Marker in Relapsed High-Grade Glioma of Children: The HIT-GBM Experience. PEDIATRIC BLOOD & CANCER, 54 (2). pp. 228-237. ISSN 1545-5009, 1545-5017
Full text not available from this repository. (Request a copy)Abstract
Background. Studies in adults with malignant glioma suggest MGMT methylation as a stratification marker. Similar data for children are sparse. We investigated the impact of MGMT methylation and expression on survival of children with high-grade glioma (HGG) registered into the German HIT-GBM database receiving temozolomide (TMZ) as part of their treatment (n=21 relapsed, n=4 primary). Procedure. Twenty-four patients were included retrospectively. methylation specific PCR (MSP), calibrated combined bisulfite restriction analysis (COBRA), and immunohistochemistry (IHC) were applied. Survival analyses were performed by Kaplan-Meier and Cox proportional-hazards models. Results. MSP demonstrated DNA methylation in 77%. Patients with a methylated MGMT promoter had a sixfold longer median EFS (P=0.015; 5.5 months vs. 0.9 months). Considering the results of calibrated COBRA, MGMT methylation was again associated with an elevated EFS (P=0.05; 10.2 months vs. 2.6 months) and OS (P=0.06; 18.7 months vs. 7.2 months) only if methylation was >14%. No difference in EFS and OS at all was noted between unmethylated and tumors methylated at low level (n = 9). Twenty-two tumors were positive by IHC, 10 showed low MGMT expression (IHC score 0-4). We did not detect any difference in EFS and OS between moderate/high-expressing tumors (IHC score 6-12) and those with low or no expression (IHC score 0-4). Conclusion. DNA methylation, but not protein expression of MGMT was associated with an increased median EFS and OS of children with relapsed HGG. MGMT methylation status warrants prospective evaluation as a stratification marker for children with HGG. Pediatr Blood Cancer 2010;54:228-237. (C) 2009 Wiley-Liss, Inc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | O-6-METHYLGUANINE-DNA METHYLTRANSFERASE GENE; PROMOTER METHYLATION ANALYSIS; GLIOBLASTOMA-MULTIFORME; DNA METHYLTRANSFERASE; IMMUNOHISTOCHEMICAL EXPRESSION; MALIGNANT GLIOMAS; CPG ISLAND; TEMOZOLOMIDE; HYPERMETHYLATION; SURVIVAL; children; DNA methylation; high-grade glioma; MGMT; temozolomide |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Aug 2020 09:08 |
| Last Modified: | 10 Aug 2020 09:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25254 |
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