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 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.