gms | German Medical Science

61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010
Joint Meeting mit der Brasilianischen Gesellschaft für Neurochirurgie am 20. September 2010

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21. - 25.09.2010, Mannheim

Analysis of p75NTR in medulloblastoma

Meeting Abstract

  • Jan Küchler - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Deutschland; Institut für Neuropathologie, Universitätsklinikum Bonn, Deutschland
  • Wolfgang Hartmann - Institut für Pathologie, Universitätsklinikum Bonn, Deutschland
  • Volker Tronnier - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Deutschland
  • Thorsten Pietsch - Institut für Neuropathologie, Universitätsklinikum Bonn, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP1772

DOI: 10.3205/10dgnc243, URN: urn:nbn:de:0183-10dgnc2437

Veröffentlicht: 16. September 2010

© 2010 Küchler 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: The classic (CMB) and the desmoplastic (DMB) subtypes represent the major medulloblastoma variants. In contrast to CMB, DMB display high levels of the low-affinity nerve growth factor receptor p75NTR. Apoptotic and proliferative functions have been attributed to p75NTR. Given reports of a better clinical course of DMB we hypothesized that p75NTR might have a “tumor suppressor” function in DMB, which is lacking in CMB.

Methods: A large panel of medulloblastomas was screened for mutations in the p75NTR coding region. p75NTR -mRNA expression and the DNA methylation status of its 5´-region were assessed. We measured p75NTR-mRNA levels in murine cerebellar granule cell precursors (GCP) after Sonic Hedgehog treatment, simulating tumorigenesis of medulloblastoma in-vitro. p75NTR immunostainings were performed in wildtype murine cerebella and medulloblastomas arising in patched heterozygous mice. Medulloblastoma cells engineered to express different variants of p75NTR were characterized flowcytometrically and morphologically by DAPI staining, analyzing the functional role of p75NTR in medulloblastoma

Results: One CMB displayed a mutation of the p75NTR coding sequence. p75NTR mRNA levels clearly delineated DMB and CMB. CpG island hypermethylation was excluded as the cause of low p75NTR expression in CMB. Sonic Hedgehog-treated GCP showed elevated p75NTR expression. Strong expression of p75NTR was detected in the external granule cell layer of wildtype mice and in murine medulloblastomas. CMB cells overexpressing p75NTR displayed a significant increase of apoptosis in flowcytometric and morphologic analysis.

Conclusions: We could exclude genetic and epigenetic alterations of p75NTR in MB, being responsible for absent p75NTR expression in CMB. Moreover we could link activated Hedgehog signaling in DMB with p75NTR expression and characterize p75NTR as a biologically relevant inductor of apoptosis in MB. Targeting the p75NTR might be a valuable target for future therapeutic interventions in MB.