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MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma
Author(s) -
Donson Andrew M.,
AddoYobo Steven O.,
Handler Michael H.,
Gore Lia,
Foreman Nicholas K.
Publication year - 2007
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.20803
Subject(s) - temozolomide , methylation , methyltransferase , medicine , o 6 methylguanine dna methyltransferase , dna methylation , dna methyltransferase , cancer research , oncology , promoter , epigenetics , glioblastoma , gene , biology , genetics , gene expression
Background Methylation of the DNA‐repair gene O 6 ‐methylguanine‐DNA methyltransferase (MGMT) causes gene silencing. This epigenetic modification has been associated with a favorable prognosis in adult patients with glioblastoma (GBM) who receive temozolomide and other alkylating agents. We explored MGMT promoter methylation in pediatric GBM and its relationship to survival and temozolomide sensitivity. Procedure We performed a retrospective study of MGMT promoter methylation in 10 pediatric GBM. The methylation status of the MGMT was determined using a 2‐stage methylation specific PCR analysis on DNA extracted from tumor specimens which had been snap frozen at surgery. The relationships between MGMT promoter methylation and patient outcome and response to temozolomide were evaluated. Results Four of our 10 pediatric patients with GBM were found to have methylation of the MGMT gene promoter. Methylation of the MGMT promoter was shown to correlate ( P = 0.0005) with survival. The average survival time for patients with methyltated MGMT was 13.7 months as compared to 2.5 months for the 6 patients with unmethylated MGMT promoter. Of the seven patients that received temozolomide, those patients that had the methylated MGMT gene promoter responded better to treatment ( P = 0.007). Conclusions As in adults, pediatric GBM patients with methylated MGMT promoter benefited from temozolomide. However, a stronger correlation with overall survival, regardless of treatment, was observed in this group of patients. These data suggest that MGMT methylation may be a prognostic factor for survival in pediatric GBM, as well as a marker for temozolomide sensitivity. Pediatr Blood Cancer © 2006 Wiley‐Liss, Inc.