Isocitrate dehydrogenase 1/2 mutational analyses and 2-hydroxyglutarate measurements in Wilms tumors

Dinesh Rakheja, Midori Mitui, Richard L. Boriack, Ralph J DeBerardinis

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background: L-2-Hydroxyglutaric aciduria (L-2-HGA) is an uncommon inborn error of metabolism, in which the patients are predisposed to develop brain tumors. Elevated levels of D-2-hydroxyglutarate have been demonstrated with malignant gliomas and myeloid leukemias associated with somatic mutations of the genes encoding NADP(+)-dependent isocitrate dehydrogenases (IDH1 and IDH2, respectively). Recently, we noted a Wilms tumor in a child with L-2-HGA. Given the accumulating evidence that both enantiomers of 2-hydroxyglutarate are associated with cellular transformation, we investigated if sporadic Wilms tumors are associated with IDH1 or IDH2 mutations or with elevated levels of 2-hydroxyglutarate.Procedure: We retrieved 21 frozen Wilms tumor tissues. In 20 cases, we sequenced exon 4 and flanking intronic regions of IDH1 and IDH2. In all 21 cases, we measured 2-hydroxyglutarate levels by liquid chromatography-tandem mass spectrometry.Results: We did not find mutations at the hot spots IDH1 codon 132 or IDH2 codon 172. Two cases (1 with favorable histology and 1 with unfavorable histology) showed heterozygous change c.211G>A (p.Val71Ile) in IDH1, a change previously reported as a mutation but listed as a single nucleotide polymorphism in the NCBI SNP database. We did not find increased levels of 2-hydroxygluatric acid in any sample.Conclusions: Our results suggest that IDH1 codon 132 or IDH2 codon 172 mutations or elevated 2-hydroxyglutarate levels do not play a role in the biology of sporadic Wilms tumors. The significance of heterozygous change c.211G>A (p.Val71Ile) in IDH1, seen in two tumors, is not clear.

Original languageEnglish (US)
Pages (from-to)379-383
Number of pages5
JournalPediatric Blood and Cancer
Volume56
Issue number3
DOIs
StatePublished - Mar 1 2011

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Keywords

  • 2-hydroxyglutarate
  • Isocitrate dehydrogenase
  • Wilms tumor

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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