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.

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.

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.

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. Pediatr Blood Cancer 2011;56:379–383. © 2010 Wiley‐Liss, Inc.