Preponderance of sonic hedgehog pathway activation characterizes adult medulloblastoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-02

AUTHORS

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

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. More... »

PAGES

229-239

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00401-010-0780-0

DOI

http://dx.doi.org/10.1007/s00401-010-0780-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052743633

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21107850


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