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Methylation profiling of
the DNA repair genes in glioblastoma multiforme and its clinical relevance
H. Kobayashi, N. Ishii, J. Ikeda, Y. Sawamura, Y. Iwasaki
Hokkaido University, Sapporo, Japan
Background. Alterations of DNA repair protein have been associated with
sensitivity to anticancer drugs, and transcriptional repression by promoter
hypermethylation is an essential role in the protein inactivation.
Recently methylation of the O6-methylguanine-DNA methyltransferase (MGMT)
promoter is an expected predictor not only of responsiveness to chemotherapy but
also of prognosis of patient with glioma.
The aim of this study was to investigate the methylation profile in DNA repair
genes, MGMT, FANCF and hMLH1, of glioblastoma multiforme and correlation between
the methylation status and outcome of the patients.
Methods. In 40 adult patients with glioblastoma multiforme treated with
surgery, irradiation, and/or chemotherapy (ACNU: n=19, cisplatin: n=11), median
age at diagnosis was 55 years old, and median overall survival time was 14
months.
Promoter hypermethylation of MGMT, hMLH1 and FANCF genes in tumor DNA was
examined using the methylation-specific PCR assay and COBRA (combined bisulfite
restriction analysis) method.
We analyzed relation between methylation status of the MGMT promoter and
survival in these patients.
Results. The hypermethylation in MGMT, FANCF and hMLH1 promoter were
detected 24 of 40 (60%), 1 of 40 (2.5%), and 0 of 40, respectively.
Kaplan-Meier analysis and log-rank test revealed no significant difference in
overall survival between patient subgroups divided by methylation status of MGMT
promoter.
Cox proportional hazard regression analysis adjusted for age of onset and extent
of surgical resection showed the MGMT promoter hypermethylation had no
significant association with overall survival time.
Conclusions. In our series, promoter hypermethylation of MGMT was not a
predictive factor for outcome, however, more controlled study would be required
to validate this result.
And it is still suggested epigenetic alteration of MGMT might influence nature
of glioblastoma compared with other DNA repair genes.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-003012,00.asp
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