CBIO-37DYNAMIC ROLE OF GTP-ENERGY METABOLISM IN GLIOMAGENESIS: DIAGNOSTIC AND THERAPEUTIC APPLICATIONS

Identification of altered metabolic pathways in glioma, compared to primary glial tissue, has the potential to aid in the development of diagnosis and targeted therapies for glioma, and would increase our understanding of the malignant nature of glioma. Alterations in glucose metabolism in gliomas have been previously described. However, it remains unknown whether other metabolic alterations could serve as diagnostic indicator due to the lack of an identifying molecular marker. Using pathological, biochemical, and metabolomics analyses, we discovered a dramatic increase in the metabolism of GTP (guanosine triphosphate), an essential energy molecule for cell proliferation, in various glioma stages. We subsequently characterize the molecular mechanism underlying this switch in GTP metabolism. We also present data that a simple immunohistochemical assay can detect this switch in GTP metabolism and potentially serves as a functional marker for metabolic reprogramming of gliomas. Our data suggest that alternate GTP metabolic pathway is a potential novel therapeutic target for glioma.