gms | German Medical Science

68th Annual Meeting of the German Society of Neurosurgery (DGNC)
7th Joint Meeting with the British Neurosurgical Society (SBNS)

German Society of Neurosurgery (DGNC)

14 - 17 May 2017, Magdeburg

The role of TET2-promotor methylation and -protein expression in pediatric posterior fossa ependymoma

Meeting Abstract

  • Daniela Pierscianek - Department of Neurosurgery, Essen, Deutschland
  • Sarah Teuber-Hanselmann - Institute of Neuropathology, University Hospital Essen, Essen, Deutschland
  • Joel Larisch - Department of Neurosurgery, Essen, Deutschland
  • Yuan Zhu - Essen, Deutschland
  • Oliver M. Müller - Universitätsklinikum Essen der Universität Duisburg-Essen, Klinik und Poliklinik für Neurochirurgie, Essen, Deutschland
  • Ulrich Sure - Universitätsklinikum Essen der Universität Duisburg-Essen, Klinik und Poliklinik für Neurochirurgie, Essen, Deutschland
  • Nicolai El Hindy - Universitätsklinikum Essen der Universität Duisburg-Essen, Klinik und Poliklinik für Neurochirurgie, Essen, Deutschland

Deutsche Gesellschaft für Neurochirurgie. Society of British Neurological Surgeons. 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS). Magdeburg, 14.-17.05.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocP 186

doi: 10.3205/17dgnc749, urn:nbn:de:0183-17dgnc7497

Published: June 9, 2017

© 2017 Pierscianek et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Ependymoma are among the most common brain tumors in children, with a predominant (60 -70 %) location in the posterior fossa. Recent studies established two main subtypes of posterior fossa ependymoma (PF): PF type A (PFA) occur in younger children, reveal a higher rate of recurrence or metastasis, are associated with a poor survival, and are located predominantly in the midline. Genetically, they show a low mutation rate und only rare copy number changes. PF type B (PFB) develop in older children, carry a better prognosis and demonstrate a high rate of copy number changes. For PFA tumors, a hypermethylation phenotype has been described. Ten-eleven translocation (TET) proteins catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosin (5-hmC) leading to DNA demethylation. Therefore, silencing of TET2 protein is supposed to lead to DNA methylation and is linked to the hypermethylation phenotype. We sought to investigate the epigenetic silencing of TET2 protein in PF and its effect on TET2 protein level.

Methods: TET2 promotor methylation in 11 pediatric PF was assessed by methylation-specific PCR using DNA extracted from FFPE tissue. Results were documented by agarose gel electrophoresis. In selected cases (due to the availability of frozen tissue), Western blot (WB) was performed to detect protein levels in PF. Additionally, clinical data comprising age, gender, days to progression, recurrence and location were analyzed.

Results: Promotor methylation of TET2 was detected in 6 of 11 children. In 6 selected cases, WB could be performed which revealed a reduced protein expression in 4 tumors. Interestingly, 3 of these 4 tumors harboured a TET2 promotor methylation. Children with TET2 methylated tumors tended to be younger (3.7 vs 4.2 years) and had a shorter time to progression (616 vs 748 days). Four patients (67%) with TET2 promotor methylation experienced recurrence and five patients (83%) had a midline location, respectively.

Conclusion: According to our results, TET2 promotor methylation is detectable in 6 of 11 (55%) PF patients, which was further associated to a reduced TET2-protein expression. Interestingly, clinical characteristics are striking similar between TET2-promoter methylated cases and hypermethylation phenotype in PFA. A prospective, multicenter investigation is mandatory, to further evaluate clinical implications of TET2 promotor methylation and PFA.