Aims: Somatic mutations in IDH1 and IDH2 are described in glioblastomas (GBMs). Mutant IDH1 and IDH2 reduce α-KG to D-2HG which accumulates, and is proposed to promote tumorigenesis. HOT catalyzes the conversion of γ-hydroxybutyrate to succinic semialdehyde in a reaction that produces D-2HG. Since increased HOT enzyme activity could lead to an accumulation of D-2HG, coupled with the fact that only a minority of GBMs carry IDH1/2 mutations and 2HG accumulation has recently been described in IDH wild-type tumors, we analyzed a set of GBM samples for mutations in the HOT gene.
Materials & methods: We screened 42 human GBM samples for mutations in HOT.
Results: No mutations in HOT were identified in the 42 GBM samples screened.
Conclusion: Mutations in the coding regions of HOT do not occur at an appreciable frequency in GBM.
Keywords: 2-hydroxyglutarate; brain; glioblastoma; glioma; hydroxyacid-oxoacid transhydrogenase; isocitrate dehydrogenase; metabolism; mutation; α-ketoglutarate.