Gene expression profile of low-grade gliomas by cDNA arrays

Hiroko Ohgaki, Huatao Huang, Hideaki Yokoo, Paul Kleihues

International Agency for Research on Cancer, Lyon, France

Background and Aim: Low-grade diffuse astrocytoma (WHO grade II) is a well-differentiated, slowly growing tumor but has an inherent tendency to progress to glioblastoma (WHO grade IV). Oligodendroglioma (WHO grade II) is susceptible to chemotherapy and carries a better prognosis. Histologic criteria for distinguishing these gliomas are somewhat subjective, with marked interobserver variability, particularly in cases of mixed oligoastrocytomas. The objective of this study was to identify novel genes differentially expressed in low-grade astrocytomas and oligodendrogliomas. Methods: We compared gene expression patterns of low-grade astrocytomas and oligodendrogliomas (11 cases each), using a cDNA array containing 1176 human cancer-related genes. As controls, normal brain (white matter of the cerebrum) and universal reference RNA (mixture of 10 human tumor cell lines) were used. Results: Of 1176 genes on the array, 180 genes were up- or down-regulated when compared to normal brain tissues in low-grade astrocytomas and/or oligodendrogliomas, and 35 genes were significantly changed only in low-grade astrocytomas and 45 genes only in oligodendrogliomas. Cluster analysis grouped these 80 genes into 5 gene clusters: Of which, two were preferentially down-regulated in oligodendrogliomas and contained several genes involved in DNA binding, repair, transcription and in signal transduction. The other three clusters were preferentially down-regulated in low-grade astrocytomas, and contained apoptosis-, immune defense- and transcription/translation-related genes. Cluster analysis of oligodendroglioma, low-grade astrocytoma, and normal brain using universal reference RNA as a control, grouped normal brain tissues and low-grade astrocytomas as distinct groups, but oligodendrogliomas were divided into two sub-groups. One group of oligodendrogliomas had an expression pattern for several genes, similar to normal brain tissue, and showed longer survival (113 vs. 35 months). Conclusions: cDNA expression patterns may aid in the distinction of gliomas of astrocytic and oligodendroglial lineage, with potential significance for diagnosis and outcome. There appear to be 2 groups of oligodendrogliomas with different gene expression patterns and prognosis.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Cancer Genomics.