title: HOTmutation screening in human glioblastomas.
abstract: OBJECTIVE
  Somatic mutations inIDH1andIDH2are 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 carryIDH1/2mutations and 2HG accumulation has recently been described inIDHwild-type tumors, we analyzed a set of GBM samples for mutations in theHOTgene.
  
  
  METHODS
  We screened 42 human GBM samples for mutations inHOT.
  
  
  RESULTS
  No mutations inHOTwere identified in the 42 GBM samples screened.
  
  
  CONCLUSIONS
  Mutations in the coding regions ofHOTdo not occur at an appreciable frequency in GBM.
authors.affiliation: Molecular & Population Genetics Laboratory, Wellcome Trust Center for Human Genetics, University of Oxford, Oxford, UK ; Department of Medical Oncology, University College London Hospitals, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Krell
authors.affiliation: Department of Medical Oncology, University College London Hospitals, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Mulholland
authors.affiliation: Division of Oncology, Department of Surgery & Cancer, Imperial Center for Translational & Experimental Medicine, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.affiliation: Molecular & Population Genetics Laboratory, Wellcome Trust Center for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.affiliation: Molecular & Population Genetics Laboratory, Wellcome Trust Center for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bardella
keywords: 2-hydroxyglutarate; brain; glioblastoma; glioma; hydroxyacid-oxoacid transhydrogenase; isocitrate dehydrogenase; metabolism; mutation; α-ketoglutarate