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. 2015;1(3):FSO22.
doi: 10.4155/fso.15.20.

HOT mutation screening in human glioblastomas

Daniel Krell  1 , Paul Mulholland  2 , Justin Stebbing  3 , Ian Tomlinson  4 , Chiara Bardella  4
Affiliations

HOT mutation screening in human glioblastomas

Daniel Krell et al. Future Sci OA. 2015.

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.

Keywords: 2-hydroxyglutarate; brain; glioblastoma; glioma; hydroxyacid-oxoacid transhydrogenase; isocitrate dehydrogenase; metabolism; mutation; α-ketoglutarate.

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Conflict of interest statement

Financial & competing interests disclosure This work was supported by the charity: Mothers and Daughters, the University College London Hospitals, Experimental Cancer Medicine Center, a grant from CRUK (C6199/A16459) and a core center grant from the Wellcome Trust (075491/Z/04). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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