Elevation of Urinary 2-Hydroxyglutarate in IDH-Mutant Glioma.

Abstract

BACKGROUND:

Recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes, which are frequent in gliomas, result in marked accumulation of the metabolic by-product 2-hydroxyglutarate (2-HG) within tumors. In other malignancies, such as acute myeloid leukemia, presence of IDH mutation is associated with elevated 2-HG levels in serum or urine compartments. Circulating 2-HG in patients with glial malignancies has not been thoroughly investigated.

METHODS:

In this study, we analyzed 2-HG levels in the serum and urine of a large set of patients with IDH-mutant and IDH-wild-type glioma, and the cerebrospinal fluid (CSF) from a subset of this cohort.

RESULTS:

We found that 2-HG was elevated in the urine of patients with IDH-mutant versus IDH-wild-type glioma, although no significant differences in 2-HG levels were observed in the serum or the small set of CSF samples obtained. Among patients with IDH-mutant glioma, 2-HG levels did not differ based on the histopathologic grade, genetic subtype (TP53 mutant or 1p/19q codeleted), presence of a canonical (IDH1 R132H) or noncanonical (any other IDH variant) mutation, or treatment type.

CONCLUSION:

Our finding suggests that urinary 2-HG is increased among patients with IDH-mutant gliomas, and may represent a future surrogate, noninvasive biomarker to aid in diagnosis, prognosis, and management.

IMPLICATIONS FOR PRACTICE:

Patients with glioma who harbor mutations in isocitrate dehydrogenase genes showed selective elevation of the oncometabolite 2-hydroxyglutarate in the urine. Similar elevations were not identified in the serum or cerebrospinal fluid. 2-Hydroxyglutarate may serve as a useful, noninvasive biomarker to stratify patients newly diagnosed with glioma with regard to prognosis and management.

• Authors: Amir T Fathi, Brian V Nahed, Seth A Wander, A John Iafrate, Darrell R Borger, Ranliang Hu, Ashraf Thabet, Daniel P Cahill, Ashley M Perry, Christelle P Joseph, Alona Muzikansky, Andrew S Chi
• Journal: The oncologist (Oncologist) Vol. 21 Issue 2 Pg. 214-9 (Feb 2016) ISSN: 1549-490X [Electronic] England
• PMID: 26834160 (Publication Type: Journal Article)
• Copyright: ©AlphaMed Press.

Chemical References

• Biomarkers, Tumor
• Glutarates
• alpha-hydroxyglutarate
• IDH2 protein, human
• Isocitrate Dehydrogenase
• IDH1 protein, human

Topics

• Adult
• Aged
• Biomarkers, Tumor (urine)
• Female
• Genotype
• Glioma (blood, genetics, pathology, urine)
• Glutarates (blood, urine)
• Humans
• Isocitrate Dehydrogenase (genetics)
• Male
• Middle Aged
• Mutation