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Methylation
of MGMT promotor, the DNA repair gene as an independent prognostic factor for
malignant glioma
S.
N. Raval, B. Gu, J. J. Raizer, M. K. Rosenblum, D. Banerjee, J. R. Bertino, L.
M. DeAngelis
Memorial
Sloan-Kettering Cancer Center, New York, NY
O6-
Methyl- guanine- DNA methyltransferase (MGMT) is responsible for resistance to
alkylating agents, and MGMT inhibition increases chemosensitivity.
MGMT activity varies widely among gliomas, but there are no known genetic
mutations of the MGMT gene to account for this variability.
Methylation of the MGMT promotor inhibits transcription, decreases intracellular
MGMT, and may be the mechanism by which MGMT expression is controlled in glioma
cells.
We investigated whether MGMT promotor methylation correlates with survival of
patients with malignant gliomas.
We examined tumor samples from 39 patients with malignant gliomas: 34 GBMs, 3
AAs, 1 anaplastic oligodendroglioma (AO) and 1 ependymoma.
There were 19 men and 20 women with mean age of 58.
Twenty-two samples were obtained at diagnosis and 17 at recurrence.
Samples were tested for MGMT promotor and promotor methylation by real time PCR.
Promotor methylation was detected in only 6 (15%).
All 6 samples were GBM and came from initial surgery specimens (27%).
Five of these patients died 1-14 months from diagnosis, mean 7.2 months; no
information is available for 1 patient.
Mean survival of the 16 newly diagnosed patients (15 GBM, 1 AO) negative for
MGMT promotor methylation was 14 months.
Contrary to prior reports, MGMT promotor methylation did not predict better
survival in the limited number of patients we studied.
However, our sample size is small and these findings warrant further study.
© Copyright 2003
American Society of Clinical Oncology All rights
reserved worldwide
Source: http://www.asco.org/ac/1,1003,_12-002489-00_18-002003-00_19-00101686-00_29-00A,00.asp?cat=CNS+Tumors&parent=
Central+Nervous+System+Tumors&returnpid=2325&SubCat_ID=4
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