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MGMT promoter hypermethylation correlates with a survival benefit from temozolomide in patients with recurrent anaplastic astrocytoma but not glioblastoma

2008; Elsevier BV; Volume: 45; Issue: 1 Linguagem: Inglês

10.1016/j.ejca.2008.09.002

1879-0852

Jan Sadones, Alex Michotte, Pieter In 'T Veld, C. Chaskis, Raf Sciot, Johan Menten, Eric Joossens, Theo Strauven, Lionel D’Hondt, D. Sartenaer, Stèphane Califice, Katja Bierau, Cecilia Svensson, Jacques De Grève, Bart Neyns,

Epigenetics and DNA Methylation

To investigate the correlation between O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and benefit from temozolomide in patients with recurrent high-grade glioma.A real-time, quantitative, methylation-specific PCR assay was performed on archival tissue blocks from patients treated with temozolomide at the first recurrence.A subgroup of 38 patients who were chemotherapy-naive at recurrence was analysed (22 glioblastoma, 12 anaplastic astrocytoma [AA] and 4 anaplastic oligoastrocytoma [AOA]); none had 1p/19q loss. Among 10 (26%) patients with a hypermethylated MGMT promoter, none experienced disease progression within the first two treatment cycles compared with 12 of 28 (43%) patients with an unmethylated promoter (p=0.016). By Cox multivariate analysis, tumour grade and MGMT promoter methylation correlated with time to progression (p<0.05); MGMT promoter methylation correlated with superior overall survival in AA/AOA but not in glioblastoma.MGMT promoter methylation predicted a survival benefit in patients with 1p/19q intact AA/AOA treated with temozolomide at recurrence.