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

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 s...

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Bibliographic Details
Published in:Brain pathology (Zurich, Switzerland) Switzerland), 2015-07, Vol.25 (4), p.429-440
Main Authors: Kleinschmidt-DeMasters, Bette K., Donson, Andrew M., Vogel, Hannes, Foreman, Nicholas K.
Format: Article
Language:English
Subjects:
Adolescent
Astrocytoma - genetics
Astrocytoma - pathology
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Child
Child, Preschool
Cohort Studies
Extracellular matrix
Female
Gene Expression
Gene Expression Profiling
Gene Ontology
glioblastoma
Humans
IMP3
Infant
Male
maturation
microarray
Mutation - genetics
Oligonucleotide Array Sequence Analysis
Pilomatrixoma - genetics
Pilomatrixoma - pathology
pilomyxoid astrocytoma
Proto-Oncogene Proteins B-raf - genetics
RNA-Binding Proteins - genetics
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Summary: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.
ISSN:1015-6305
1750-3639
DOI:10.1111/bpa.12239