| Autor: |
Sciuscio D., Diserens A. C., van Dommelen K., Martinet D., Jones G., Janzer R. C., Pollo C., Hamou M. F., Kaina B., Stupp R., Levivier M., Hegi M. E. |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
Clin Cancer Res |
| Popis: |
PURPOSE: Quantitative methylation specific tests suggest that not all cells in a glioblastoma with detectable promoter methylation of the O6 methylguanine DNA methyltransferase (MGMT) gene carry a methylated MGMT allele. This observation may indicate cell subpopulations with distinct MGMT status raising the question of the clinically relevant cutoff of MGMT methylation therapy. Epigenetic silencing of the MGMT gene by promoter methylation blunts repair of O6 methyl guanine and has been shown to be a predictive factor for benefit from alkylating agent therapy in glioblastoma. EXPERIMENTAL DESIGN: Ten paired samples of glioblastoma and respective glioblastoma derived spheres (GS) cultured under stem cell conditions were analyzed for the degree and pattern of MGMT promoter methylation by methylation specific clone sequencing MGMT gene dosage chromatin status and respective effects on MGMT expression and MGMT activity. RESULTS: In glioblastoma MGMT methylated alleles ranged from 10 to 90. In contrast methylated alleles were highly enriched (100 of clones) in respective GS even when 2 MGMT alleles were present with 1 exception ( |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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