IDH pathway-related molecular and cellular changes
tumor
PROLIFERATION, REGRESSION, TUMOR, INFILTRATION
Staining of resected tumor tissue with an antibody against the Ki-67 antigen, a marker for tumor cell proliferation, showed a positive correlation between tumor cell proliferation and tumor 2-HG concentrations (Fig. We observed an inverse correlation between tumor 2-HG concentrations and DNA 5-hydroxymethylcytosine (5hmC) content (Fig. Genome-wide RNA expression profiling and data analysis, using established molecular pathway annotations (Molecular Signatures Database, C2 Pathways)Among gene sets that represent specific biological states or processes (Molecular Signatures Database, Hallmark Pathways), the interferon (IFN)-α and IFN-γ pathways were the most highly upregulated pathways at low tumor 2-HG concentrations. In contrast, genes associated with cell-cycle progression (G2M_Checkpoint) were suppressed at low tumor 2-HG levels (Fig. Using linear regression analysis, we identified 762 genes that were induced or repressed in response to 2-HG suppression (Extended Data Fig. Examination of formalin-fixed, paraffin-embedded (FFPE) tumor tissue from the resection showed an inverse correlation between tumor 2-HG and tumor-infiltrating CD3Matched-pair analysis from surgery 1 (archival tumor tissue from previous surgery) and surgery 2 (on-treatment surgery) suggested that more complete tumor 2-HG suppression was required to promote tumor infiltration with CD3