Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate

Area of Science:

• Biochemistry
• Oncology
• Metabolomics

Background:

• Elevated D-2-hydroxyglutarate (D-2-HG) is linked to IDH1/IDH2 mutations in gliomas and myeloid leukemias.
• L-2-hydroxyglutaric aciduria, a metabolic disorder, increases brain tumor predisposition.
• The role of 2-hydroxyglutarate in sporadic cancers lacking IDH mutations is largely unexplored.

Purpose of the Study:

• To investigate whether sporadic cancers, specifically papillary thyroid carcinoma (PTC), exhibit elevated 2-hydroxyglutarate (2-HG) levels.
• To determine if these elevated levels are associated with the absence of common IDH1 and IDH2 mutations.
• To explore the potential of 2-HG as a cancer biomarker.

Main Methods:

• Collected 15 pairs of PTC and adjacent non-neoplastic thyroid tissue, and 14 pairs of hyperplastic nodules (HN) and adjacent non-hyperplastic thyroid tissue.
• Confirmed the absence of IDH1 and IDH2 mutations in exon 4 of all samples.
• Quantified D-2-HG and L-2-HG levels using liquid chromatography-tandem mass spectrometry.

Main Results:

• Papillary thyroid carcinoma (PTC) tissues showed significantly higher levels of both D-2-HG and L-2-HG compared to normal thyroid tissue.
• PTC tissues had significantly higher D-2-HG levels compared to hyperplastic nodules (HN).
• No significant difference in D-2-HG/L-2-HG ratios was observed between HNs and normal thyroid tissue.

Conclusions:

• Elevated D-2-HG and L-2-HG levels are present in sporadic papillary thyroid carcinoma, irrespective of IDH1/IDH2 mutations.
• Further research is warranted to validate 2-hydroxyglutarate as a potential cancer biomarker in PTC.
• The biological role of elevated 2-hydroxyglutarate in thyroid cancer development requires further investigation.