Distinctive molecular profiles of high-grade and low-grade gliomas based on oligonucleotide microarray analysis

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