Preponderance of sonic hedgehog pathway activation characterizes adult medulloblastoma

Hani Al-Halabi, Andre Nantel, Almos Klekner, Marie Christine Guiot, Steffen Albrecht, Peter Hauser, Miklos Garami, Laszlo Bognar, Peter Kavan, Noha Gerges, Margret Shirinian, David Roberge, Thierry Muanza, Nada Jabado

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32 Citations (Scopus)

Abstract

Medulloblastoma (MB) represents approximately 4% of adult brain tumours, and as such is a poorly studied disease. Although many adult MB are treated using paediatric MB protocols, the reported outcomes are inferior to those observed in children. It remains unclear whether biologic differences underlie these clinical observations. We investigated the molecular characteristics of 31 adult MB. Twelve and 19 adult MB were respectively examined using Affymetrix-HG-U133-plus-2.0-genechips and immunohistochemical analyses. 26/31 (84%) of adult MB examined by gene expression and/or immunohistochemical analysis showed evidence of sonic hedgehog (SHH) pathway activation. A comparison of adult and paediatric MB showed that most adult tumours cluster within the SHH-active subgroup of paediatric MB. The preponderance of SHH activity in adult MB tumours was also shown by positive SFRP1 immunostaining in 16/19 adult paraffin-embedded adult MB tumour blocks. A smaller proportion of adult tumours exhibited evidence of WNT pathway activation, as confirmed by nuclear β-catenin staining (9.7%; 3/31). Notably, we found PTCH1 gene mutation in 4/8 samples tested. Similar to children, adult MB has abnormalities in developmental signalling pathways including SHH and WNT. Importantly, we found a preponderance of SHH pathway activation amongst MB tumours in adults. This SHH signature does not appear to correlate with a long-term favourable outcome. Differences in molecular profiles exist between adult and paediatric SHH-driven MB and further investigations are needed to better characterize age-related molecular profiles in this subgroup.

Original languageEnglish
Pages (from-to)229-239
Number of pages11
JournalActa neuropathologica
Volume121
Issue number2
DOIs
Publication statusPublished - Feb 1 2011

Keywords

  • Adult medulloblastoma
  • Microarray gene expression profiling
  • Molecular subgroups
  • Sonic hedgehog signalling
  • Targeted therapy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Al-Halabi, H., Nantel, A., Klekner, A., Guiot, M. C., Albrecht, S., Hauser, P., Garami, M., Bognar, L., Kavan, P., Gerges, N., Shirinian, M., Roberge, D., Muanza, T., & Jabado, N. (2011). Preponderance of sonic hedgehog pathway activation characterizes adult medulloblastoma. Acta neuropathologica, 121(2), 229-239. https://doi.org/10.1007/s00401-010-0780-0