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Lookup NU author(s): Professor Steven CliffordORCiD
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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.
Author(s): Northcott PA, Hielscher T, Dubuc A, Mack S, Shih D, Remke M, Al-Halabi H, Albrecht S, Jabado N, Eberhart CG, Grajkowska W, Weiss WA, Clifford SC, Bouffet E, Rutka JT, Korshunov A, Pfister S, Taylor MD
Publication type: Article
Publication status: Published
Journal: Acta Neuropathologica
Print publication date: 17/06/2011
ISSN (print): 0001-6322
ISSN (electronic): 1432-0533
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