gms | German Medical Science

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Frequent down-regulation of bone morphogenetic protein (BMP) genes 2, 4 and 6 in murine and human medulloblastomas

Meeting Abstract

  • presenting/speaker Petra Zipper - Uniklinik Düsseldorf, Neuropathologie, Düsseldorf, Germany
  • Frank Grünheck - Uniklinik Düsseldorf, Kardiologie, Düsseldorf, Germany
  • Guido Reifenberger - Uniklinik Düsseldorf, Neuropathologie, Düsseldorf, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP3.2

DOI: 10.3205/12dgnn046, URN: urn:nbn:de:0183-12dgnn0463

Published: September 11, 2012

© 2012 Zipper et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-ß superfamily and function as important regulators of cell growth, differentiation, and apoptosis in a variety of cell types. Inactivation of BMP pathway genes has been implicated in the pathogenesis of several cancers. We investigated the potential role of altered BMP expression in the medulloblastoma, the most common malignant brain tumor in children. Expression levels and promoter methylation status of BMP2, BMP4 and BMP6 were determined in 12 murine medulloblastomas derived from Ptch1+/- mice and 20 human medulloblastomas (11 classic and 9 desmoplastic medulloblastomas). Significantly reduced mRNA expression levels of all three genes relative to normal cerebellar tissue were found in all murine and the classic human medulloblastomas. DNA methylation analysis using sequencing of sodium bisulfit-modified DNA revealed aberrant methylation of the promoter regions of BMP2 and BMP4 in murine medulloblastomas and of BMP4 in human medulloblastomas.In vitro functional analyses showed that BMP2 overexpression reduced cell viability, apoptotic rate and clonogenicity of murine medulloblastoma cells in vitro, with no obvious effect on tumor cell proliferation. Our data suggest that BMP genes function as tumor suppressors and that their reduced expresssion contributes to the development medulloblastoma in mice and man.