Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct

• Verfasst von: Northcott, Paul A. [VerfasserIn]
• Verfasst von: Hielscher, Thomas [VerfasserIn]
• Verfasst von: Dubuc, Adrian [VerfasserIn]
• Verfasst von: Mack, Stephen [VerfasserIn]
• Verfasst von: Shih, David [VerfasserIn]
• Verfasst von: Remke, Marc [VerfasserIn]
• Verfasst von: Al-Halabi, Hani [VerfasserIn]
• Verfasst von: Albrecht, Steffen [VerfasserIn]
• Verfasst von: Jabado, Nada [VerfasserIn]
• Verfasst von: Eberhart, Charles G. [VerfasserIn]
• Verfasst von: Grajkowska, Wieslawa [VerfasserIn]
• Verfasst von: Weiss, William A. [VerfasserIn]
• Verfasst von: Clifford, Steven C. [VerfasserIn]
• Verfasst von: Bouffet, Eric [VerfasserIn]
• Verfasst von: Rutka, James T. [VerfasserIn]
• Verfasst von: Korshunov, Andrey [VerfasserIn]
• Verfasst von: Pfister, Stefan [VerfasserIn]
• Verfasst von: Taylor, Michael D. [VerfasserIn]
• Titel: Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct
• Verf.angabe: 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
• E-Jahr: 2011
• Jahr: 17 June 2011
• Umfang: 10 S.
• Fussnoten: Gesehen am 29.09.2022
• Titel Quelle: Enthalten in: Acta neuropathologica
• Ort Quelle: Berlin : Springer, 1961
• Jahr Quelle: 2011
• Band/Heft Quelle: 122(2011), 2, Seite 231-240
• ISSN Quelle: 1432-0533
• DOI: doi:10.1007/s00401-011-0846-7
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Genomics
• Sach-SW: Medulloblastoma
• Sach-SW: Molecular classification
• Sach-SW: Sonic hedgehog
• K10plus-PPN: 1817780328

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.