Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate
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Elevated levels of d-2-hydroxyglutarate (d-2-HG) occur in gliomas and myeloid leukemias associated with mutations of IDH1 and IDH2. l-2-Hydroxyglutaric aciduria, an inherited metabolic disorder, predisposes to brain tumors. Therefore, we asked whether sporadic cancers, without IDH1 or IDH2 hot-spot mutations, show elevated 2-hydroxyglutarate levels. We retrieved 15 pairs of frozen papillary thyroid carcinoma (PTC) and adjacent non-neoplastic thyroid, and 14 pairs of hyperplastic nodule (HN) and adjacent non-hyperplastic thyroid. In all lesions, exon 4 sequencing confirmed the absence of known mutations of IDH1 and IDH2. We measured 2-hydroxyglutarate by liquid chromatography-tandem mass spectrometry. Compared to normal thyroid, PTCs had significantly higher d-2-HG and l-2-hydroxyglutarate (l-2-HG) levels, and compared to HNs, PTCs had significantly higher d-2-HG levels. d-2-HG/l-2-HG levels were not significantly different between HNs and normal thyroid. Further studies should clarify if elevated 2-hydroxyglutarate in PTC may be useful as cancer biomarker and evaluate the role of 2-hydroxyglutarate in cancer biology.
Keywords2-Hydroxyglutarate Isocitrate dehydrogenase Papillary thyroid carcinoma Thyroid cancer
- 10.Rogers RE, Deberardinis RJ, Klesse LJ, Boriack RL, Margraf L, Rakheja D. Wilms tumor in a child with l-2-hydroxyglutaric aciduria. Pediatr Dev Pathol. 2010.Google Scholar
- 17.Murugan AK, Bojdani E, Xing M. Identification and functional characterization of isocitrate dehydrogenase 1 (IDH1) mutations in thyroid cancer. Biochem Biophys Res Commun. 2010.Google Scholar
- 34.Read MH, Bonamy C, Laloum D, Belloy F, Constans JM, Guillois B, et al. Clinical, biochemical, magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1 H MRS) findings in a fourth case of combined d- and l-2 hydroxyglutaric aciduria. J Inherit Metab Dis. 2005;28:1149–50.CrossRefPubMedGoogle Scholar