title: Pilomyxoid Astrocytoma (PMA) Shows Significant Differences in Gene Expression vs. Pilocytic Astrocytoma (PA) and Variable Tendency Toward Maturation to PA.
abstract: Pilomyxoid astrocytomas (PMAs) manifest a more aggressive clinical course than pilocytic astrocytomas (PAs). Development of effective therapies demands a better biological understanding of PMA. We first conducted gene expression microarray analysis of 9 PMA and 13 PA 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 PMAs and six PAs, all supratentorial/hypothalamic/chiasmal. Clinical outcome of PMAs 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 PA in some areas and de-differentiation to glioblastoma in others. A surviving child has undergone multiple surgical debulking, with progressive maturation to PA over time. Ontology-enrichment analysis identified overexpression in PMAs of extracellular matrix and mitosis-related genes. Genes overexpressed in PMA vs. PA, ranked according to fold-change, included developmental genes H19, DACT2, extracellular matrix collagens (COL2A1; COL1A1) and IGF2BP3 (IMP3), the latter previously identified as an adverse prognostic factor in PMA and PA.
authors.affiliation: Department of Pathology, The University of Colorado School of Medicine, Aurora, CO.|Department of Neurosurgery, The University of Colorado School of Medicine, Aurora, CO.|Department of Neurology, The University of Colorado School of Medicine, Aurora, CO.
authors.forename: Bette K
authors.initials: BK
authors.lastname: Kleinschmidt-DeMasters
authors.affiliation: Department of Pediatrics, The University of Colorado School of Medicine, Aurora, CO.|Children's Hospital Colorado, Aurora, CO.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Donson
authors.affiliation: Department of Pathology, Stanford University, Palo Alto, CA.
authors.forename: Hannes
authors.initials: H
authors.lastname: Vogel
authors.affiliation: Department of Neurosurgery, The University of Colorado School of Medicine, Aurora, CO.|Department of Neurology, The University of Colorado School of Medicine, Aurora, CO.|Department of Pediatrics, The University of Colorado School of Medicine, Aurora, CO.|Children's Hospital Colorado, Aurora, CO.
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Foreman
mesh_terms: D000293:Adolescent; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D063990:Gene Ontology; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D018296:Pilomatrixoma / Q000235:genetics* / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics
chemical_list: C498780:IGF2BP3 protein, human; D016601:RNA-Binding Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: IMP3; glioblastoma; maturation; microarray; pilomyxoid astrocytoma