MOLECULAR CLASSIFICATION OF HUMAN GLIAL TUMORS

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The studies presented in this proposal are designed to provide molecular reagents to assist in the classification of human glial tumors. Astrocytes and oligodendrocytes are the predominant glial cells of the central nervous system and are believed to represent the transformed cells of origin in most gliomas. The classification of these tumors is currently based solely on histological criteria. Our preliminary studies indicate that the RNA transcripts that encode the proteins of myelin should serve as sensitive markers of tumors of oligodendrocyte origin. Moreover, these studies also suggest that a subset of human glial tumors currently believed to be of astrocytic origin may actually be of oligodendroglial origin. We speculate, based on our studies with a transformed oligodendrocyte cell line, that the phenotypic properties of CNS glial tumors are influenced by the environment in which these tumors reside. The environment of these tumors is altered due to the disruption of the blood-brain barrier and the infiltration of immune cells, which secrete a multitude of cytokines. We propose to correlate the molecular and histological phenotype of human CNS gliomas with the degree of lymphocyte infiltration into these tumors and the local concentration of various cytokines. In turn, these results will be correlated with the clinical outcome of the patients. Together, these studies should provide us with molecular reagents that should help in the classification of human gliomas such that the clinical course of afflicted individuals may be more accurately predicted and treatment protocols designed accordingly.