gms | German Medical Science

60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit den Benelux-Ländern und Bulgarien

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

24. - 27.05.2009, Münster

Global analysis of the glioblastoma epigenome identifies different major classes of epigenetically-regulated genes

Meeting Abstract

  • R. Martinez - Klinik für Neurochirurgie, Universitätsklinikum Göttingen
  • V. Rohde - Klinik für Neurochirurgie, Universitätsklinikum Göttingen
  • C. Bock - Klinik für Neurochirurgie, Universitätsklinikum Göttingen
  • S. Ropero - Spanish National Cancer Centre, Madrid
  • G. Schackert - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden
  • M. Esteller - Spanish National Cancer Centre, Madrid

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP04-02

DOI: 10.3205/09dgnc282, URN: urn:nbn:de:0183-09dgnc2826

Veröffentlicht: 20. Mai 2009

© 2009 Martinez et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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Objective: Molecular investigation of glioblastoma multiforme has indicated a significant, increasing role for epigenetic events in the pathogenesis of this malignancy. To assess the glioblastoma epigenome more comprehensively, we have undertaken a genome-wide investigation to identify genes which display evidence of methylation-dependent regulation.

Methods: 90 consecutive glioblastoma patients were investigated. All patients had undergone surgery and adjuvant therapy. DNA methylation profiling was performed using methylation bead arrays. Methylation was assessed at 1.536 CpG sites in 371 genes (one to nine sites per gene). The amount of bisulfite-modified target DNA that hybridizes to each spot of the chip was quantified and standardized to a maximum of 1.0 (the likelihood of hypermethylation of this gene promoter is almost 100%) and a minimum of 0.0 (the likelihood of promoter hypermethylation is almost 0%). The assay was validated by analyzing normal brain tissue and the glioblastoma tumor cell line U87.

Results: The median age at diagnosis was 60.72 years (range: 52.6–70.3; SD: 8.8). The median survival time after surgery was 9.6 months (range: 3.0–93.6; SD: 15.84). We have observed different major classes of epigenetically regulated genes in tumor tissue: a) normally methylated genes whose methylation reflects somatic patterns observed in the cerebrum; b) genes showing loss of methylation as a consequence of a global tumor demethylation (n= 21); c) tumor specific methylated genes which display enhanced methylation levels compared to the normal brain tissue (n=12).

Conclusions: Our data reveal a more diverse and expansive glioblastoma epigenome than previously understood and provide strong evidence that the methylation status of specific genes is of major relevance in GBM pathogenesis.