Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate

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 nonneoplastic 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.