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Expression Analysis of Juvenile Pilocytic Astrocytomas by Oligonucleotide Microarray Reveals Two Potential Subgroups

¹ Texas Children's Cancer Center, ² Departments of Pediatrics, ³ Neurosurgery, and ⁴ Pathology, Baylor College of Medicine, Houston, Texas

Requests for reprints: K-K. Wong, Department of Pediatrics, Hematology-Oncology, Baylor College of Medicine, Room 1030.09, Feigin Center, 1102 Bates Street, Houston, TX 77030. Phone: 832-824-4373; Fax: 832-825-4038. E-mail: kkwong{at}bcm.tmc.edu

Juvenile pilocytic astrocytoma (JPA) is one of the most common brain tumors in children. The expression profiles of 21 JPAs, determined using Affymetrix GeneChip U133A, were compared with subjects with normal cerebella. The genes involved in neurogenesis, cell adhesion, synaptic transmission, central nervous system development, potassium ion transport, protein dephosphorylation, and cell differentiation were found to be significantly deregulated in JPA. These 21 JPAs were further clustered into two major groups by unsupervised hierarchical clustering using a set of 848 genes with high covariance (0.5-10). Supervised analysis with Significance Analysis of Microarrays software between these two potential subgroups identified a list of significant differentially expressed genes involved in cell adhesion, regulation of cell growth, cell motility, nerve ensheathment, and angiogenesis. Immunostaining of myelin basic protein on paraffin sections derived from 18 incompletely resected JPAs suggests that JPA without myelin basic protein–positively stained tumor cells may have a higher tendency to progress.

Key Words: juvenile pilocytic astrocytoma • oligonucleotide array • neurogenesis • axonal guidance • 00-00-02 Brain/central nervous system cancers • 04-08-00 Molecular Oncology • 00-00-23 Pediatric cancers • 02-12-00 Gene Expression, Chromatin Regulation, and Oncogenomics • 02-07-01 Gene expression profiling

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