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Brain Pathol. 2015 Jul;25(4):429-40. doi: 10.1111/bpa.12239. Epub 2015 Jan 27.

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

Author information

1
Department of Pathology, The University of Colorado School of Medicine, Aurora, CO.
2
Department of Neurosurgery, The University of Colorado School of Medicine, Aurora, CO.
3
Department of Neurology, The University of Colorado School of Medicine, Aurora, CO.
4
Department of Pediatrics, The University of Colorado School of Medicine, Aurora, CO.
5
Children's Hospital Colorado, Aurora, CO.
6
Department of Pathology, Stanford University, Palo Alto, CA.

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.

KEYWORDS:

IMP3; glioblastoma; maturation; microarray; pilomyxoid astrocytoma

PMID:
25521223
PMCID:
PMC4470883
DOI:
10.1111/bpa.12239
[Indexed for MEDLINE]
Free PMC Article

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