Minimally Invasive Detection of IDH1 Mutation With Cell-Free Circulating Tumor DNA and D-2-Hydroxyglutarate, D/L-2-Hydroxyglutarate Ratio in Gliomas

Tuna G., Dal-Bekar N. E., Akay A., Ruksen M., Islekel S., İşlekel G. H.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, vol.81, no.7, pp.502-510, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 81 Issue: 7
  • Publication Date: 2022
  • Doi Number: 10.1093/jnen/nlac036
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.502-510
  • Keywords: Cell-free circulating tumor DNA, D, L-2-hydroxyglutarate ratio, D-2-hydroxyglutarate, Gliomas, IDH1 mutation, L-2-hydroxyglutarate, Liquid biopsy, CENTRAL-NERVOUS-SYSTEM, URINARY 2-HYDROXYGLUTARATE, CLASSIFICATION, PLASMA
  • Dokuz Eylül University Affiliated: Yes


Isocitrate dehydrogenase-1 (IDH1) mutation is accepted as one of the earliest events in tumorigenesis in gliomas. This mutation causes preferential accumulation of D- relative to L-enantiomer of 2-hydroxyglutarate (2-HG). Minimally invasive techniques to detect IDH1 mutation may prove useful for clinical practice. We adopted 2 different diagnostic approaches to detect IDH1 mutation status in glioma patients: Evaluation of D- and L-2-HG levels in cerebrospinal fluid (CSF), urine, and plasma, and identification of IDH1 mutation using cell-free circulating tumor DNA (ctDNA) in CSF and plasma. Forty-nine glioma patients in different stages were included. Levels of D- and L-2-HG were determined using liquid chromatography-tandem mass spectrometry; IDH1 R132H mutation was determined by digital-PCR. D-2-HG levels and D/L-2-HG ratio (rDL) in CSF and rDL in plasma were significantly higher in the mutant group than in the wild-type group (p = 0.029, 0.032, 0.001, respectively). The IDH1 mutation detection rates in CSF- and plasma-ctDNA were 63.2% and 25.0%, respectively. These data indicate that D-2-HG values in CSF and rDL in plasma and CSF can be considered as significant contributors to the identification of IDH1 mutation status. In addition, detection of IDH1 mutation in CSF-ctDNA from glioma patients provides a basis for future use of ctDNA for minimally invasive clinical assessment of gliomas.