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HOT mutation screening in human glioblastomas.

ABSTRACT: 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. We screened 42 human GBM samples for mutations in HOT. No mutations in HOT were identified in the 42 GBM samples screened. Mutations in the coding regions of HOT do not occur at an appreciable frequency in GBM.

SUBMITTER: Krell D

PROVIDER: S-EPMC4776344 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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<i>HOT</i> mutation screening in human glioblastomas.

Krell Daniel D Mulholland Paul P Stebbing Justin J Tomlinson Ian I Bardella Chiara C

Future science OA 20150101 3

<h4>Aims</h4>Somatic mutations in <i>IDH1</i> and <i>IDH2</i> 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 <i>IDH1/2</i> mutations and 2HG accumulation has rece ...[more]

PMID: 26948489

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