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Kleinschmidt‐DeMasters, Bette K.; Donson, Andrew M.; Vogel, Hannes; Foreman, Nicholas K.

Pilomyxoid Astrocytoma (PMA) Shows Significant Differences in Gene Expression vs. Pilocytic Astrocytoma (PA) and Variable Tendency Toward Maturation to PA

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  • Medientyp: E-Artikel
  • Titel: Pilomyxoid Astrocytoma (PMA) Shows Significant Differences in Gene Expression vs. Pilocytic Astrocytoma (PA) and Variable Tendency Toward Maturation to PA
  • Beteiligte: Kleinschmidt‐DeMasters, Bette K.; Donson, Andrew M.; Vogel, Hannes; Foreman, Nicholas K.
  • Erschienen: Wiley, 2015
  • Erschienen in: Brain Pathology
  • Sprache: Englisch
  • DOI: 10.1111/bpa.12239
  • ISSN: 1015-6305; 1750-3639
  • Schlagwörter: Neurology (clinical) ; Pathology and Forensic Medicine ; General Neuroscience
  • Entstehung:
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Pilomyxoid astrocytomas (<jats:styled-content style="fixed-case">PMAs</jats:styled-content>) manifest a more aggressive clinical course than pilocytic astrocytomas (<jats:styled-content style="fixed-case">PAs</jats:styled-content>). Development of effective therapies demands a better biological understanding of <jats:styled-content style="fixed-case">PMA</jats:styled-content>. We first conducted gene expression microarray analysis of 9 <jats:styled-content style="fixed-case">PMA</jats:styled-content> and 13 <jats:styled-content style="fixed-case">PA</jats:styled-content> from infra‐ and supratentorial sites. Unsupervised hierarchical clustering analysis demonstrated that tumors are grouped according to anatomic site, not diagnosis. Gene expression profiles were then contrasted between eight <jats:styled-content style="fixed-case">PMAs</jats:styled-content> and six <jats:styled-content style="fixed-case">PAs</jats:styled-content>, all supratentorial/hypothalamic/chiasmal. Clinical outcome of <jats:styled-content style="fixed-case">PMAs</jats:styled-content> varied, with four out of four patients with diencephalic syndrome succumbing to disease, one of whom showed bulky metastatic leptomeningeal spread at autopsy, with bimodal maturation to <jats:styled-content style="fixed-case">PA</jats:styled-content> in some areas and de‐differentiation to glioblastoma in others. A surviving child has undergone multiple surgical debulking, with progressive maturation to <jats:styled-content style="fixed-case">PA</jats:styled-content> over time. Ontology‐enrichment analysis identified overexpression in <jats:styled-content style="fixed-case">PMAs</jats:styled-content> of extracellular matrix and mitosis‐related genes. Genes overexpressed in <jats:styled-content style="fixed-case">PMA</jats:styled-content> vs. <jats:styled-content style="fixed-case">PA</jats:styled-content>, ranked according to fold‐change, included developmental genes <jats:styled-content style="fixed-case"><jats:italic>H19</jats:italic></jats:styled-content>, <jats:styled-content style="fixed-case"><jats:italic>DACT2</jats:italic></jats:styled-content>, extracellular matrix collagens (<jats:styled-content style="fixed-case">COL2A1</jats:styled-content>; <jats:styled-content style="fixed-case">COL1A1</jats:styled-content>) and <jats:styled-content style="fixed-case"><jats:italic>IGF2BP3</jats:italic></jats:styled-content> (<jats:styled-content style="fixed-case">IMP3</jats:styled-content>), the latter previously identified as an adverse prognostic factor in <jats:styled-content style="fixed-case">PMA</jats:styled-content> and <jats:styled-content style="fixed-case">PA</jats:styled-content>.</jats:p>
  • Zugangsstatus: Freier Zugang