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Preponderance of sonic hedgehog pathway activation characterizes adult medulloblastoma

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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.

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Acknowledgments

This work was supported by the Cole Foundation and the Montreal Children’s Hospital Research Institute (N.J.). N.J. and T.M. are the recipients of a Chercheur Boursier award from Fonds de Recherche en Sante du Quebec. We would like to thank Dr Janusz Rak and Annie Huang for critical reading of this manuscript. We would also like to thank the staff of the Genome Quebec sequencing platform, particularly Aurelie Masurel and Pierre Lepage, for active participation in this study.

Conflict of interest

The authors state no conflict of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, Montreal General Hospital, McGill University Health Centre, Montreal, Canada

    Hani Al-Halabi, David Roberge & Thierry Muanza

  2. Biotechnology Research Institute, National Research Council of Canada, Montreal, Canada

    Andre Nantel

  3. Department of Neurosurgery, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    Almos Klekner & Laszlo Bognar

  4. Department of Pathology, Montreal Neurological Institute, McGill University Health Center, Montreal, Canada

    Marie-Christine Guiot

  5. Department of Pathology, Montreal Children’s Hospital, McGill University Health Center, Montreal, Canada

    Steffen Albrecht

  6. 2nd Department of Paediatrics, Faculty of Medicine, Semmelweis University, Budapest, Hungary

    Peter Hauser & Miklos Garami

  7. Department of Oncology, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada

    Peter Kavan

  8. Department of Oncology, Montreal Neurological Hospital, McGill University Health Centre, Montreal, Canada

    Peter Kavan & Thierry Muanza

  9. Departments of Paediatrics and Human Genetics, McGill University Health Center, Montreal, Canada

    Noha Gerges, Margret Shirinian & Nada Jabado

  10. Montreal Children’s Hospital Research Institute, 4060 Ste Catherine West, PT-239, Montreal, QC, H3Z 2Z3, Canada

    Nada Jabado

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  1. Hani Al-Halabi
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  2. Andre Nantel
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Correspondence to Nada Jabado.

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H. Al-Halabi and A. Nantel equally contributed to the manuscript.

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Al-Halabi, H., Nantel, A., Klekner, A. et al. Preponderance of sonic hedgehog pathway activation characterizes adult medulloblastoma. Acta Neuropathol 121, 229–239 (2011). https://doi.org/10.1007/s00401-010-0780-0

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  • DOI: https://doi.org/10.1007/s00401-010-0780-0

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