Tumor Biology

, Volume 32, Issue 2, pp 325–333

Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate

  • Dinesh Rakheja
  • Richard L. Boriack
  • Midori Mitui
  • Shama Khokhar
  • Shelby A. Holt
  • Payal Kapur
Research Article

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.

Keywords

2-Hydroxyglutarate Isocitrate dehydrogenase Papillary thyroid carcinoma Thyroid cancer 

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Dinesh Rakheja
    • 1
    • 2
  • Richard L. Boriack
    • 1
  • Midori Mitui
    • 1
  • Shama Khokhar
    • 1
  • Shelby A. Holt
    • 3
  • Payal Kapur
    • 2
  1. 1.Department of Pathology, Children’s Medical CenterDallasUSA
  2. 2.Department of PathologyUniversity of Texas (UT) Southwestern Medical CenterDallasUSA
  3. 3.Department of SurgeryUniversity of Texas (UT) Southwestern Medical CenterDallasUSA

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