Preponderance of sonic hedgehog pathway activation characterizes adult medulloblastoma

Al-Halabi, Hani and Nantel, Andre and Klekner, Almos and Guiot, Marie-Christine and Albrecht, Steffen and Hauser, Peter and Garami, Miklos and Bognar, Laszlo and Kavan, Peter and Gerges, Noha and Shirinian, Margret and Roberge, David and Muanza, Thierry and Jabado, Nada (2011) Preponderance of sonic hedgehog pathway activation characterizes adult medulloblastoma. Acta Neuropathologica, 121 (2). pp. 229-239. ISSN 0001-6322

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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 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.

Item Type: Article
Uncontrolled Keywords: Adult medulloblastoma, Sonic hedgehog signalling, Microarray gene expression profiling, Targeted therapy, Molecular subgroups
Subjects: R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkológia
Depositing User: Dr. Álmos Klekner
Date Deposited: 26 Sep 2014 18:10
Last Modified: 26 Sep 2014 18:10

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