Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-08

AUTHORS

Paul A. Northcott, Thomas Hielscher, Adrian Dubuc, Stephen Mack, David Shih, Marc Remke, Hani Al-Halabi, Steffen Albrecht, Nada Jabado, Charles G. Eberhart, Wieslawa Grajkowska, William A. Weiss, Steven C. Clifford, Eric Bouffet, James T. Rutka, Andrey Korshunov, Stefan Pfister, Michael D. Taylor

ABSTRACT

Recent integrative genomic approaches have defined molecular subgroups of medulloblastoma that are genetically and clinically distinct. Sonic hedgehog (Shh) medulloblastomas account for one-third of all cases and comprise the majority of infant and adult medulloblastomas. To discern molecular heterogeneity among Shh-medulloblastomas, we analyzed transcriptional profiles from four independent Shh-medulloblastoma expression datasets (n = 66). Unsupervised clustering analyses demonstrated a clear distinction between infant and adult Shh-medulloblastomas, which was reliably replicated across datasets. Comparison of transcriptomes from infant and adult Shh-medulloblastomas revealed deregulation of multiple gene families, including genes implicated in cellular development, synaptogenesis, and extracellular matrix maintenance. Furthermore, metastatic dissemination is a marker of poor prognosis in adult, but not in pediatric Shh-medulloblastomas. Children with desmoplastic Shh-medulloblastomas have a better prognosis than those with Shh-medulloblastomas and classic histology. Desmoplasia is not prognostic for adult Shh-medulloblastoma. Cytogenetic analysis of a large, non-overlapping cohort of Shh-medulloblastomas (n = 151) revealed significant over-representation of chromosome 10q deletion (P < 0.001) and MYCN amplification (P < 0.05) in pediatric Shh cases compared with adults. Adult Shh-medulloblastomas harboring chromosome 10q deletion, 2 gain, 17p deletion, 17q gain, and/or GLI2 amplification have a much worse prognosis as compared to pediatric cases exhibiting the same aberrations. Collectively, our data demonstrate that pediatric and adult Shh-medulloblastomas are clinically, transcriptionally, genetically, and prognostically distinct. More... »

PAGES

231-240

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00401-011-0846-7

DOI

http://dx.doi.org/10.1007/s00401-011-0846-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051667195

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21681522


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