Notably, wild-type IDH via onco-metabolite (R)-2-hydroxyglutarate is implicated in HIF1α regulation and consequently ECM stiffness regulation; in patients with recurrent IDH-mutant tumor, ECM stiffness was noted to increase comparing initial diagnosis and associated increased TNC expression suggesting a mechanosignaling-induced tumor aggression (70). This evidence concerns the gene HIF1A and neoplasm.