Gene Expression Based Classification of Glial Tumors

Stanley F. Nelson
UCLA Medical Center

Abstract:

Astrocytic brain tumors are among the most lethal and morbid tumors of adults, often occurring during the prime of life. The current system of diagnosis and classification of brain tumors is partially predictive of outcomes, and remains based primarily upon morphologic criteria. Although recent work has shown a number of genetic differences which are critical in the oncogenesis and progression of astrocytic tumors, there is insufficient data to develop a molecular classification system. The availability of cDNA clones, large amounts of sequence, data and the technology for cDNA arrays provides a platform for the large scale analysis of gene expression in astrocytoma. We propose to identify a set of genes that will allow the molecular characterization of brain tumors by using cDNA microarray technology. Using a flexible microarray format will enable us to easily alter the arrayed genes whose expression patterns are most informative allowing us to create cost-effective glial tumor-related reagents. It is our central hypothesis that a much more detailed analysis of the genes that are expressed in astrocytomas will provide a more precise prognostic ability, subgroup patients for optimal treatment, and help identify appropriate therapeutic targets, subgroups patients for optimal treatment 1) To determine the optimal means of sampling low grade astrocytomas, anaplastic astrocytomas, and glioblastoma multiformes, to determine the degree of molecular heterogeneity within astrocytic tumors, to determine whether the heterogeneity is greater between tumors than within an individual tumor at each gene, and to determine the level of variance of each gene on the microarray. 2) To determine the gene expression profiles of 120 excisional glioma and meningioma brain tumor biopsies to develop a reclassification of the tumors based on gene expression profiles. 3) To develop a set of genes with prognostic importance in low grade astrocytomas. 4) To validate the importance of the genes from specific aims 2 and 3 in the prognosis of low grade astrocytomas.