title: Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate.
abstract: 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.
authors.affiliation: Department of Pathology, Children's Medical Center, Dallas, TX, USA. dinesh.rakheja@utsouthwestern.edu
authors.forename: Dinesh
authors.initials: D
authors.lastname: Rakheja
authors.forename: Richard L
authors.initials: RL
authors.lastname: Boriack
authors.forename: Midori
authors.initials: M
authors.lastname: Mitui
authors.forename: Shama
authors.initials: S
authors.lastname: Khokhar
authors.forename: Shelby A
authors.initials: SA
authors.lastname: Holt
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005977:Glutarates / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism*; D016606:Thyroid Nodule / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005977:Glutarates; D007656:Ketoglutaric Acids; C019417:alpha-hydroxyglutarate; D018698:Glutamic Acid; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human