gms | German Medical Science

67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12. - 15. Juni 2016, Frankfurt am Main

Different methylation pattern in pilocytic astrocytoma

Meeting Abstract

  • Christoph Sippl - Klinik für Neurochirurgie, Universitätskliniken des Saarlandes, Homburg/Saar, Germany
  • Stefanie Urbschat - Klinik für Neurochirurgie, Universitätskliniken des Saarlandes, Homburg/Saar, Germany
  • Joo Yin Kim - Neuropathologie, Universitätskliniken des Saarlandes, Homburg/Saar, Germany
  • Joachim Oertel - Klinik für Neurochirurgie, Universitätskliniken des Saarlandes, Homburg/Saar, Germany
  • Ralf Ketter - Klinik für Neurochirurgie, Universitätskliniken des Saarlandes, Homburg/Saar, Germany

Deutsche Gesellschaft für Neurochirurgie. 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS). Frankfurt am Main, 12.-15.06.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocMO.10.03

doi: 10.3205/16dgnc042, urn:nbn:de:0183-16dgnc0423

Veröffentlicht: 8. Juni 2016

© 2016 Sippl et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objective: Pilocytic astrocytomas are WHO grade I gliomas occurring mainly during childhood and adolescence. Promoter hypermethylation of tumor suppressor genes is a very common mechanism in CNS neoplasms which is generally associated with their transcriptional silencing.

Method: Using MS-PCR, we analyzed the methylation status of the tumor suppressor genes p15, p16, RB1, and MGMT in n = 18 pilocytic astrocytomas. Furthermore, all tumour samples were tested for the R132H mutation of the IDH1 gene by use of immunohistochemical staining. The results of the MGMT methylation analysis were correlated with the individual clinical and demographical data as well as with the progression-free (PFS) and overall survival (OS).

Results: For the MGMT gene, methylation frequency was 44.5% (8/18). Interestingly, when stratified for the MGMT methylation status, the group of methylated pilocytic astrocytomas showed a significantly shortened PFS in the Kaplan-Meier curve compared to their unmethylated counterparts (11.75 Months vs. 74.0 Months; p = 0.041; univariate log rank test). Each of the 18 pilocytic astrocytoma specimens presented unmethylated in the investigated promoter regions of p16 and RB1. For the p15 gene, 1/18 tumor sample showed a positive methylation signal (5.6%). This single case presented with an extraordinary aggressive clinical course including frequent local recurrences with meningeal metastases but without tumor upgrading.

Conclusions: Epigenetic mechanisms, in particular the promoter methylation of the MGMT and p15 genes, contrary to the perception of literature that pilocytic astrocytomas are commonly unmethylated, may obviously have an impact on the clinical course in pilocytic astrocytoma disease.