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Adult medulloblastoma momprises three major molecular variants

Purpose - - Medulloblastoma is a rare primary brain tumor in adults, whereas it constitutes the most common malignant brain tumor in children. Integrated genomics approaches revealed at least four distinct disease variants in children. The aim of this study was to investigate molecular subtypes and...

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Main Authors: Remke, Marc (Author) , Hielscher, Thomas (Author) , Northcott, Paul A. (Author) , Witt, Hendrik (Author) , Ryzhova, Marina (Author) , Wittmann, Andrea (Author) , Benner, Axel (Author) , Deimling, Andreas von (Author) , Scheurlen, Wolfram (Author) , Perry, Arie (Author) , Croul, Sidney (Author) , Kulozik, Andreas (Author) , Lichter, Peter (Author) , Taylor, Michael D. (Author) , Pfister, Stefan (Author) , Korshunov, Andrey (Author)
Format: Article (Journal)
Language:English
Published: May 31, 2011
In: Journal of clinical oncology
Year: 2011, Volume: 29, Issue: 19, Pages: 2717-2723
ISSN:1527-7755
DOI:10.1200/JCO.2011.34.9373
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1200/JCO.2011.34.9373
Verlag, lizenzpflichtig, Volltext: https://ascopubs.org/doi/10.1200/JCO.2011.34.9373
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Author Notes:Marc Remke, Thomas Hielscher, Paul A. Northcott, Hendrik Witt, Marina Ryzhova, Andrea Wittmann, Axel Benner, Andreas von Deimling, Wolfram Scheurlen, Arie Perry, Sidney Croul, Andreas E. Kulozik, Peter Lichter, Michael D. Taylor, Stefan M. Pfister, and Andrey Korshunov
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Summary:Purpose - - Medulloblastoma is a rare primary brain tumor in adults, whereas it constitutes the most common malignant brain tumor in children. Integrated genomics approaches revealed at least four distinct disease variants in children. The aim of this study was to investigate molecular subtypes and their prognostic implication in a large cohort of adult medulloblastomas as the biology in this age group remains poorly understood. - - Patients and Methods - - We combined transcriptome and DNA copy number analyses for 28 adult medulloblastomas. Statistical and bioinformatic tools were applied to discover distinct molecular variants. Clinical and molecular characteristics of each biologic subtype were validated using immunohistochemistry on a tissue microarray derived from an independent patient cohort of adult medulloblastomas (n = 103). - - Results - - Gene expression profiles revealed three distinct molecular variants with stable subtype separation using the 300 most varying transcripts. Distinct demographics, genetics, transcriptome, and prognosis were noted for each subtype of adult medulloblastoma. Immunohistochemistry revealed aberrant activation of the sonic hedgehog (SHH) pathway in over half of adult medulloblastomas constituting a promising molecular therapeutic target. In contrast, subtype C tumors, which comprise a robust subtype in childhood medulloblastoma are only exceptionally seen in adult cohorts. Notably, adult subtype D and Wnt/wingless tumors were associated with worse prognosis than pediatric cohorts, whereas survival for SHH tumors was similar for both age groups. - - Conclusion - - The transcriptome of adult medulloblastomas differs considerably from pediatric counterparts, both in terms of tumor biology and prognostic impact. Therefore, age-specific classification is required and must be adapted for use in clinical trials of adult medulloblastoma.
Item Description:Gesehen am 15.09.2022
Physical Description:Online Resource
ISSN:1527-7755
DOI:10.1200/JCO.2011.34.9373

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