gms | German Medical Science

62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

Intratumoral variation of MGMT promoter methylation in glioblastoma – a regional quantitative analysis

Meeting Abstract

  • L. Dörner - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • K. Hattermann - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • A. Nabavi - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • U. Malkus-Coskun - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • H.M. Mehdorn - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • J. Held-Feindt - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocMI.05.05

DOI: 10.3205/11dgnc214, URN: urn:nbn:de:0183-11dgnc2140

Published: April 28, 2011

© 2011 Dörner et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Objective: Hypermethylation of the DNA repair gene O6-methylguanine DNA methyltranferase (MGMT) has been associated with an increased survival of patients with glioblastomas receiving standard chemotherapy with the alkylating agent temozolomide. In the latest chemotherapy trials, the MGMT promoter methylation status has been used as an inclusion or exclusion criterion. For diagnosis the standard methylation specific PCR (MSP) is routinely being used. With the MSP a homogeneous MGMT promoter hypermethylation within different regions of malignant gliomas has been shown. Recently a new methylation-specific quantitative PCR (MSQP) has been developed to analyze the hypermethylation in more detail. The goal of this study has been to evaluate whether the homogeneity of the promoter methylation exists not only in a qualitative (MSP) but also in a quantitative (MSQP) manner.

Methods: 17 adult patients with glioblastomas were included in the study. 3 biopsies were separately taken within each tumor in a distance of at least 1cm as documented by neuronavigational screenshots. The biopsies were then split and taken for histopathological documentation and MSQP.

Results: Of the patients 14 were newly diagnosed and 3 recurrent glioblastomas, all tumors samples were histopathologically verified tumor tissue. 9 patients showed a significant variation of the MSQP tested methylation of the different tumor samples. The tumors of the other 8 patients had only minimal or no intratumoral variation of the MSQP tested methylation, and at the same time a non relevant or no methylation of the MGMT promoter.

Conclusions: Our result prove that we cannot rely solely on a single MSQP for a correct determination of the methylation status. The correlation of MSQP and MSP will determine the relevance of the presented results for adjuvant therapy and prognosis. The results may be an explanation for the diversity of patient outcome seen with malignant glioma patients and methylated MGMT promoter status measured with MSP.