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[Cancer Research 61, 6885-6891, September 15, 2001]
© 2001 American Association for Cancer Research

Molecular Biology and Genetics

Distinctive Molecular Profiles of High-Grade and Low-Grade Gliomas Based on Oligonucleotide Microarray Analysis1

David S. Rickman, Miroslav P. Bobek, David E. Misek, Rork Kuick, Mila Blaivas, David M. Kurnit, Jeremy Taylor and Samir M. Hanash2

Departments of Pediatrics [D. S. R., D. E. M., R. K., D. M. K., S. M. H.], Surgery [M. P. B.], Pathology [M. B.], Human Genetics [D. M. K.], and The Comprehensive Cancer Center [M. B., J. T., S. M. H.], University of Michigan Medical School, Ann Arbor, Michigan 48109

Astrocytomas are heterogeneous intracranial glial neoplasms ranging from the highly aggressive malignant glioblastoma multiforme (GBM) to the indolent, low-grade pilocytic astrocytoma. We have investigated whether DNA microarrays can identify gene expression differences between high-grade and low-grade glial tumors. We compared the transcriptional profile of 45 astrocytic tumors including 21 GBMs and 19 pilocytic astrocytomas using oligonucleotide-based microarrays. Of the ~6800 genes that were analyzed, a set of 360 genes provided a molecular signature that distinguished between GBMs and pilocytic astrocytomas. Many transcripts that were increased in GBM were not previously associated with gliomas and were found to encode proteins with properties that suggest their involvement in cell proliferation or cell migration. Microarray-based data for a subset of genes was validated using real-time quantitative reverse transcription-PCR. Immunohistochemical analysis also localized the protein products of specific genes of interest to the neoplastic cells of high-grade astrocytomas. Our study has identified a large number of novel genes with distinct expression patterns in high-grade and low-grade gliomas.




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