Format

Send to

Choose Destination
Clin Cancer Res. 2016 Dec 15;22(24):6256-6265. Epub 2016 Jun 23.

Selective Detection of the D-enantiomer of 2-Hydroxyglutarate in the CSF of Glioma Patients with Mutated Isocitrate Dehydrogenase.

Author information

1
Department of Neurosurgery, Emory University, Atlanta, Georgia.
2
Department of Human Genetics, Emory University, Atlanta, Georgia.
3
Department of Radiology, School of Medicine, Emory University, Atlanta, Georgia.
4
Winship Cancer Institute, Emory University, Atlanta, Georgia.
5
Penn State College of Medicine, Hershey, Pennsylvania.
6
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts.
7
University of Medical Center of Mainz, Mainz, Germany.
8
Hunstman Cancer Institute, University of Utah, Salt Lake City, Utah.
9
University of California, San Diego, La Jolla, California.
10
Department of Neurosurgery, Emory University, Atlanta, Georgia. evanmei@emory.edu.
11
Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia.

Abstract

PURPOSE:

Elevation in D-2-Hydroxyglutarate (D-2HG) has recently emerged as a mandatory byproduct of mutated Isocitrate Dehydrogenase (IDH) genes 1 and 2 in glioma patients. The goal of the present study was to demonstrate the feasibility of detection of elevated levels of D-2HG in the cerebrospinal fluid (CSF) of glioma patients that carry point substitutions in the IDH gene.

EXPERIMENTAL DESIGN:

We developed a mass spectrometry (MS)-based platform to detect and quantify the D- and L-forms of 2HG in the CSF of glioma patients. Three independent cohorts of patients were analyzed, comprising a total of 176 samples derived from 84 patients. The levels of D- and L-2HG were used to stratify patients into IDH wild-type or IDH-mutated groups using an empirically obtained threshold of 0.69 μmol/L.

RESULTS:

Using this platform, a greater than 17-fold mean increase in D-2HG was observed in the CSF of patients with IDH mutant versus wild-type gliomas. The means for the D-2HG levels in CSF were 0.427 μmol/L in wild-type and 7.439 μmol/L in mutant groups. The C statistic for the receiver operator curve was 0.938, with 84% sensitivity, 90% specificity, and 89% accuracy to detect D-2HG. The levels of D- and L-2HG in CSF from wild-type patients varied by location of CSF draw (cisternal > ventricular > lumbar).

CONCLUSIONS:

Our findings demonstrate that the CSF of patients harboring IDH mutant gliomas contain increased levels of D-2HG, which can be reliably detected with a MS-based platform. Clin Cancer Res; 22(24); 6256-65. ©2016 AACR.

PMID:
27340277
PMCID:
PMC5443654
DOI:
10.1158/1078-0432.CCR-15-2965
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center