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See Latest ArticlesExtent of MGMT promoter methylation correlates with outcome in glioblastomas given temozolomide and radiotherapy
British Journal of Cancer, 06/22/09
Dunn J et al. - In a trial to investigate O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation in glioblastomas treated with temozolomide and radiotherapy, these data indicate that MGMT methylation is prognostically significant in glioblastomas given chemoradiotherapy in the routine clinic; the extent of methylation may be used to provide additional prognostic stratification.
Methods- Quantitative methylation data at individual CpG sites were obtained by pyrosequencing for 109 glioblastomas.
- Median overall survival (OS) was 12.4 mos with 2-yr survival of 17.9%.
- Pyrosequencing data were reproducible with archival samples yielding data for all glioblastomas.
- Variation in methylation patterns of discrete CpG sites and intratumoral methylation heterogeneity were observed.
- 58 of 109 glioblastomas showed average methylation >non-neoplastic brain in at least 1 clinical sample; 86% had homogeneous methylation status in multiple samples.
- Methylation was an independent prognostic factor associated with prolonged progression-free survival (PFS) and OS.
- Cases with methylation >35% had the longest survival (median PFS 19.2; OS 26.2 mos, 2-yr survival of 59.7%).
- Significant differences in PFS were seen between those with intermediate or high methylation and unmethylated cases, whereas cases with low, intermediate, or high methylation all showed significantly different OS.
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