HOT mutation screening in human glioblastomas

Abstract

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. Genetic changes in genes called IDH have been shown to occur regularly in brain tumors. These changes result in the production of a chemical called D-2HG which accumulates to a high level in cells and is thought to damage normal cells, causing them to become cancer cells. Genetic changes in other genes may also result in the production of D-2HG and cause cancer in the same way as changes in IDH do. One such gene is called HOT. This study investigated whether genetic changes in HOT could be found in brain tumors.