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Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate

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Tumor Biology

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.

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Authors and Affiliations

  1. Department of Pathology, Children’s Medical Center, Dallas, TX, USA

    Dinesh Rakheja, Richard L. Boriack, Midori Mitui & Shama Khokhar

  2. Department of Pathology, University of Texas (UT) Southwestern Medical Center, MC 9073, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA

    Dinesh Rakheja & Payal Kapur

  3. Department of Surgery, University of Texas (UT) Southwestern Medical Center, Dallas, TX, USA

    Shelby A. Holt

Authors
  1. Dinesh Rakheja
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  2. Richard L. Boriack
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  3. Midori Mitui
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Correspondence to Dinesh Rakheja.

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Rakheja, D., Boriack, R.L., Mitui, M. et al. Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate. Tumor Biol. 32, 325–333 (2011). https://doi.org/10.1007/s13277-010-0125-6

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  • DOI: https://doi.org/10.1007/s13277-010-0125-6

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