Abstract | BACKGROUND: METHODS: Quantitative methylation data at individual CpG sites were obtained by pyrosequencing for 109 glioblastomas. RESULTS: Median overall survival (OS) was 12.4 months with 2-year 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. A total of 58 out of 109 glioblastomas showed average methylation >non-neoplastic brain in at least one 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 more than 35% had the longest survival (median PFS 19.2; OS 26.2 months, 2-year 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. CONCLUSIONS: These data indicate that MGMT methylation is prognostically significant in glioblastomas given chemoradiotherapy in the routine clinic; furthermore, the extent of methylation may be used to provide additional prognostic stratification.
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Authors | J Dunn, A Baborie, F Alam, K Joyce, M Moxham, R Sibson, D Crooks, D Husband, A Shenoy, A Brodbelt, H Wong, T Liloglou, B Haylock, C Walker |
Journal | British journal of cancer
(Br J Cancer)
Vol. 101
Issue 1
Pg. 124-31
(Jul 07 2009)
ISSN: 1532-1827 [Electronic] England |
PMID | 19536096
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Alkylating
- Dacarbazine
- O(6)-Methylguanine-DNA Methyltransferase
- Temozolomide
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Topics |
- Adolescent
- Adult
- Aged
- Antineoplastic Agents, Alkylating
(therapeutic use)
- Brain Neoplasms
(enzymology, genetics, therapy)
- Cell Line, Tumor
- Chemotherapy, Adjuvant
- DNA Methylation
- Dacarbazine
(analogs & derivatives, therapeutic use)
- Female
- Glioblastoma
(enzymology, genetics, therapy)
- Humans
- Male
- Middle Aged
- O(6)-Methylguanine-DNA Methyltransferase
(genetics)
- Promoter Regions, Genetic
- Radiotherapy
- Temozolomide
- Treatment Outcome
- Young Adult
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