gms | German Medical Science

59th Annual Meeting of the German Society of Neurosurgery (DGNC)
3rd Joint Meeting with the Italian Neurosurgical Society (SINch)

German Society of Neurosurgery (DGNC)

1 - 4 June 2008, Würzburg

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Promoter Hypermethylation of O6-Methylguanine DNA Methyltransferase (MGMT) in primary and recurrent glioma

Promotorhypermethylierung der O6-Methylguanin DNA Methyltransferase (MGMT) bei Gliomen und deren Rezidiven

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  • corresponding author N. Vogt - Klinik für Allgemeine Neurochirugie, Labor für Onkologische Neurochirurgie, Klinikum der Universität zu Köln
  • G. Röhn - Klinik für Allgemeine Neurochirugie, Labor für Onkologische Neurochirurgie, Klinikum der Universität zu Köln
  • M. Löhr - Klinik für Allgemeine Neurochirugie, Labor für Onkologische Neurochirurgie, Klinikum der Universität zu Köln
  • J. A. Hampl - Klinik für Allgemeine Neurochirugie, Labor für Onkologische Neurochirurgie, Klinikum der Universität zu Köln

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocMO.13.03

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2008/08dgnc126.shtml

Published: May 30, 2008

© 2008 Vogt et al.
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Outline

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Objective: MGMT is a repair protein that in DNA removes alkylating substances from the O6-guanine. This results in resistence against mutagenic and cytotoxic damage, caused by certain carcinogenes and chemotherapeutics. The high variability of the MGMT amount in different tumors leads to an unequal response of alkylating substances. Therefore, the control of this reaction is of particular clinical interest. In the present study we investigated promoter hypermethylation and expression of the MGMT gene in primary gliomas with different WHO grades and their respective recurrences.

Methods: Hypermethylation of the MGMT promoter region was examined in fresh frozen tumor tissue taken during surgery from 20 patients with primary gliomas and at least two corresponding recurrent tumors. Using methylation-specific PCR (MSP) of bisulfite-modified DNA, MGMT methylation has been investigated semiquantitatively in 65 tissue samples. In addition, in all samples the expression of the MGMT protein was examined by immunohistochemistry.

Results: In our fresh frozen tissue bank, out of 3021 patients we found 20 patients, where tissue of a primary glioma and at least two corresponding recurrences were available. The observation span was 1 to 12 years with a median of 5,5 years. There was a distinct increase in the methylation status in 11 out of 13 patients with a malignization of the recurrent glioma (WHO°II to WHO°III), whereas recurrent low grade gliomas confirmed previous results. The progression from a WHO°III to a WHO°IV tumor (4/4) again corresponded with an increase in the percentage of methylation, but to a much smaller extent than from WHO°II to WHO°III. In contrast, recurrences of all primary and secondary glioblastomas (8/8) showed a stable or reduced methylation of the MGMT promoter region.

Conclusions: The absolute amount of MGMT methylation showed a high rate of interindividual variation. Nevertheless in the individual patient, we found a direct correlation of an increase in the methylation status to tumor progression in most patients, especially during malignization of the tumors (WHO°II to WHO°III or WHO°IV, respectively). Interestingly, in glioblastoma a distinct regressive development could be observed during recurrence. This is in accordance with the clinical observation of an increased resistance against alkylating substances in glioblastoma recurrences.