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- Publisher Website: 10.1007/s00401-011-0846-7
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- PMID: 21681522
- WOS: WOS:000292780500009
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Article: Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct
Title | Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct |
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Authors | |
Keywords | Genomics Medulloblastoma Molecular classification Sonic hedgehog |
Issue Date | 2011 |
Citation | Acta Neuropathologica, 2011, v. 122, n. 2, p. 231-240 How to Cite? |
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. © 2011 Springer-Verlag. |
Persistent Identifier | http://hdl.handle.net/10722/313947 |
ISSN | 2023 Impact Factor: 9.3 2023 SCImago Journal Rankings: 4.720 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Northcott, Paul A. | - |
dc.contributor.author | Hielscher, Thomas | - |
dc.contributor.author | Dubuc, Adrian | - |
dc.contributor.author | MacK, Stephen | - |
dc.contributor.author | Shih, David | - |
dc.contributor.author | Remke, Marc | - |
dc.contributor.author | Al-Halabi, Hani | - |
dc.contributor.author | Albrecht, Steffen | - |
dc.contributor.author | Jabado, Nada | - |
dc.contributor.author | Eberhart, Charles G. | - |
dc.contributor.author | Grajkowska, Wieslawa | - |
dc.contributor.author | Weiss, William A. | - |
dc.contributor.author | Clifford, Steven C. | - |
dc.contributor.author | Bouffet, Eric | - |
dc.contributor.author | Rutka, James T. | - |
dc.contributor.author | Korshunov, Andrey | - |
dc.contributor.author | Pfister, Stefan | - |
dc.contributor.author | Taylor, Michael D. | - |
dc.date.accessioned | 2022-07-06T11:28:33Z | - |
dc.date.available | 2022-07-06T11:28:33Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Acta Neuropathologica, 2011, v. 122, n. 2, p. 231-240 | - |
dc.identifier.issn | 0001-6322 | - |
dc.identifier.uri | http://hdl.handle.net/10722/313947 | - |
dc.description.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. © 2011 Springer-Verlag. | - |
dc.language | eng | - |
dc.relation.ispartof | Acta Neuropathologica | - |
dc.subject | Genomics | - |
dc.subject | Medulloblastoma | - |
dc.subject | Molecular classification | - |
dc.subject | Sonic hedgehog | - |
dc.title | Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1007/s00401-011-0846-7 | - |
dc.identifier.pmid | 21681522 | - |
dc.identifier.pmcid | PMC4538327 | - |
dc.identifier.scopus | eid_2-s2.0-79960842253 | - |
dc.identifier.volume | 122 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 231 | - |
dc.identifier.epage | 240 | - |
dc.identifier.eissn | 1432-0533 | - |
dc.identifier.isi | WOS:000292780500009 | - |