Preponderance of sonic hedgehog pathway activation characterizes adult medulloblastoma

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 SHHactive subgroup of paediatric MB. The preponderance of SHH activity in adult MB tumours was also shown by positive SFRP1 immunostaining in 16/19 adult paraffinembedded adult MB tumour blocks. A smaller proportion of adult tumours exhibited evidence of WNT pathway activation, as confirmed by nuclear b-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 H. Al-Halabi and A. Nantel equally contributed to the manuscript. Electronic supplementary material The online version of this article (doi:10.1007/s00401-010-0780-0) contains supplementary material, which is available to authorized users. H. Al-Halabi  D. Roberge  T. Muanza Department of Radiation Oncology, Montreal General Hospital, McGill University Health Centre, Montreal, Canada A. Nantel Biotechnology Research Institute, National Research Council of Canada, Montreal, Canada A. Klekner  L. Bognar Department of Neurosurgery, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary M.-C. Guiot Department of Pathology, Montreal Neurological Institute, McGill University Health Center, Montreal, Canada S. Albrecht Department of Pathology, Montreal Children’s Hospital, McGill University Health Center, Montreal, Canada P. Hauser  M. Garami 2nd Department of Paediatrics, Faculty of Medicine, Semmelweis University, Budapest, Hungary P. Kavan Department of Oncology, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada P. Kavan  T. Muanza Department of Oncology, Montreal Neurological Hospital, McGill University Health Centre, Montreal, Canada N. Gerges  M. Shirinian  N. Jabado Departments of Paediatrics and Human Genetics, McGill University Health Center, Montreal, Canada N. Jabado (&) Montreal Children’s Hospital Research Institute, 4060 Ste Catherine West, PT-239, Montreal, QC H3Z 2Z3, Canada e-mail: nada.jabado@mcgill.ca 123 Acta Neuropathol (2011) 121:229–239 DOI 10.1007/s00401-010-0780-0 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.