Role of succinate dehydrogenase deficiency and oncometabolites in gastrointestinal stromal tumors

Figure 1 Mutations in metabolic enzymes produce oncometabolites. Shown are genetic mutations in tricarboxylic acid (TCA) cycle enzymes (underscored) involved in generating oncometabolites (bold). Isocitrate dehydrogenase (IDH) mutations are neomorphic, producing proteins with the modified function of producing D-2-hydroxyglutarate (D-2HG), while succinate dehydrogenase (SDH) and fumarate hydrase (FH) mutations are loss-of-function mutations that lead to the accumulation of succinate and fumarate, respectively. α-KG: α-ketoglutarate.

Figure 2 Metabolic enzyme mutations lead to the accumulation of oncometabolites, which competitively inhibit α-ketoglutarate-dependent dioxygenases. α-KG: α-ketoglutarate; AMLs: Acute myeloid leukemias; D-2HG: D-2-hydroxyglutarate; FH: Fumarate hydrase; HLRCC: Hereditary leiomyomatosis and renal cell cancer; IDH: Isocitrate dehydrogenase; LGGs: Low-grade gliomas; SDH: Succinate dehydrogenase.