Foci of Tumor Heterogeneity in Diffuse Low-Grade Gliomas

Background: Diffuse low-grade gliomas (DLGG) are slow-growing primary-cancer of the brain and spinal cord. They represent up to 15% of the developing tumors in those organs with fatal outcome for the patients because of their evolution. The reasons for this transformation towards more malignant tumors still remain ill defined. Previously, the research team in neuro oncology at Montpellier University Hospital found foci of tumor heterogeneity within 20 to 30 % of the patients developing a DLGG and published their results. The investigators assumed that those foci represent the early beginning of the transformation from a diffuse low-grade glioma to a glioblastoma, tumor with highly malignant cells and a life expectancy of two years in average for the patient. Methods: The investigators selected adult patients with no prior surgery nor neuro oncology treatment when enrolled. They presented a specific mutation for an enzyme of the metabolism named IDH1, standing for Isocitrate Dehydrogenase 1, found in 70% of DLGG. Patients were also selected because they presented foci of tumor heterogeneity. After obtaining their consent, the investigators studied by immunohistochemistry the pathways deregulated between the DLGG and the foci. The investigators also extracted RNAs, molecules expressing the life and metabolism of tumor cells, and compared them to know what genes were differentially expressed between the DLGG and the foci. All RNAs were tested for quality control prior to be processed further. The investigators then studied 8 patients with compliance with ethics, authorizations and institutional guidelines. Genes of interest were studied in vitro to assess their functions. The investigators found a barely described enzyme of the catabolism of the phosphoethanolamines and discovered a new anti-proliferative tumor-role for it. •Discussion: The investigators first showed that foci have a higher percentage of p-STAT3+ cells which indicates STAT3 pathway activation in th