Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate

Dinesh Rakheja, Richard L. Boriack, Midori Mitui, Shama Khokhar, Shelby A Holt, Payal Kapur

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)325-333
Number of pages9
JournalTumor Biology
Issue number2
StatePublished - Apr 1 2011


  • 2-Hydroxyglutarate
  • Isocitrate dehydrogenase
  • Papillary thyroid carcinoma
  • Thyroid cancer

ASJC Scopus subject areas

  • Cancer Research


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