gms | German Medical Science

63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

13. - 16. Juni 2012, Leipzig

Differential DNA methylation in long-term surviving GBM patients

Meeting Abstract

  • A. Mock - Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg; Abteilung für Epigenomik und Krebsrisikofaktoren, Deutsches Krebsforschungszentrum, Heidelberg
  • R. Warta - Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
  • P. Schmezer - Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
  • C. Plass - Abteilung für Epigenomik und Krebsrisikofaktoren, Deutsches Krebsforschungszentrum, Heidelberg
  • C.H. Herold-Mende - Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
  • A. Unterberg - Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocFR.01.08

DOI: 10.3205/12dgnc172, URN: urn:nbn:de:0183-12dgnc1726

Veröffentlicht: 4. Juni 2012

© 2012 Mock 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

Text

Objective: Despite unfavorable diagnosis, 3–5% of glioblastoma patients show long-term survival of 36 months or longer after diagnosis. Recent publications indicate that this survival benefit bases on altered gene expression. Epigenetic modifications, e.g. DNA methylation are known to be one cause of these alterations. But with the exception of a few genes such as MGMT, correlations with survival are still pending. We therefore aimed to identify novel differentially methylated genes that on the one hand serve as a predictive signature but on the other hand unveil further insights into glioma biology.

Methods: We applied Methyl-CpG Immunoprecipitation (MCIp) and CpG island microarray analysis on 15 glioblastoma short-term (STS) and 14 long-term survivor (LTS) tissue samples to obtain comparative genome wide methylation profiles. Patients were highly selected to exclude known prognostic parameters (age, resection extent, completed radio- and chemotherapy, MGMT promotor hypermethylation, IDH1 mutation). Subsequent quantitative methylation analysis of the candidate genes were performed by MassARRAY technique (Sequenom).

Results: Statistical analysis of the CpG island microarray data revealed a set of 74 genes to be significantly differentially methylated in at least 2 positive neighboring probes on the array. Intriguingly, DNA methylation occurred more frequently in LTS (66/74). The top 16 of these genes were validated in an independent approach by MassARRAY. Differential methylation could be confirmed for 15 of 16 identified genes including the hypoxia marker CA9 and the DNA repair enzyme NEIL1. 5 gene loci showed methylation differences between the STS and LTS patients of 5–10%, 9 between 10–20% and one even over 25%. Validation in an independent study sample and association with mRNA expression is currently tested.

Conclusions: Our results revealed a signature of 15 novel differentially methylated genes in long-term surviving GBM patients. The observation that 14 genes are significantly hypermethylated in LTS indicates that these genes are associated with a better response to chemo- or radiotherapy. This hypothesis is reinforced by identification of NEIL1, yet another DNA repair enzyme such as MGMT.