Gliomas in patients express variations in antigens. Antigenic variations of a similar nature occur during explanation of gliomas, but the changes occur more rapidly during explanation than in situ. The objective of my research is to determine mechanisms of this variation. This is relevant to major biologic questions about cellular lineage and may be relevant to the development of effective therapeutic strategies for treating gliomas. Hypotheses to be tested are: 1. Heterogeneity of antigenic phenotype and DNA ploidy increases with increased grade of malignancy of glioma tissue. There is a subpopulation of cells of nonglial cell linkage in all or most high grade glioma tissues which express sarcomatous markers. 2. The neoplastic cells which seed heterogenous growth in the earliest phase of culture are the same as cells present in glioma tissue at first biopsy. 3. Changes in antigens or ploidy which occur in gliomas over time are due to overgrowth of specific cells from a relatively small number of neoplastic subpopulations at least two of which have vastly different constellations of antigens reflecting different lineage. 4. Changes in antigens are due to modulation of gene expression within the glioma cell. The methods to test these hypotheses have been selected for their capabilities to analyse both human glioma tissue and cultures. First the diversity of antigen experession in tissue and in culture prior to passage will be characterized by immunofluorescence and simultaneously correlated with quantitative DNA microdensitometry by computerized image analysis. Results will be related to degree of malignancy of the gliomas. Later quantitation of these cellular subpopulations over time will determine the contribution of overgrowth of these characterized subpopulations to antigenic variation. The contribution of modulation of gene expression to this antigenic variation will be assessed with quantitative assays of RNA and protein production. Proliferation in athymic rats will be employed to confirm neoplasia in antigenically distinct cell populations when sufficient cells are available. This will develop an understanding of the progressive changes in antigen expression, genotype and neoplastic potential in these glioma cells.
