Article
IDH mutation prediction in glioma – a multimodal diagnostic approach
Prädiktionder IDH-Mutation in Gliomen – ein multimodales diagnostisches Konzept
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Published: | June 26, 2020 |
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Objective: Non-invasive and accurate diagnostic techniques to detect isocitrate dehydrogenase (IDH) mutant glioma may have great potential in routine clinical practice. With this in mind, we performed a multimodal diagnostic approach to predict the IDH mutation status in newly diagnosed gliomas using: 2-Hydroxyglutarate (2HG) single-voxel spectroscopy (SVS), IDH-mutant cell-free tumor-derived DNA (tDNA) in the CSF, in addition to 2HG (D- and L- forms) concentration measurement in the CSF.
Methods: 2HG MR spectroscopy was obtained in 18 patients with a newly diagnosed IDH-mutant glioma. The IDH1/2 mutation status was determined using next-generation sequencing in the glioma tissue and in the CSF-tDNA (n=55). In addition, in a subset of patients (n=15), 2HG concentrations were measured in the CSF using liquid chromatography-tandem mass spectrometry (LCMS). Ratios of D-and L-2HG were used to evaluate differences in 2HG accumulation in tumors.
Results: IDH mutations were correctly predicted using the 2HG spectroscopy with 93.3% sensitivity (17/18, 95% CI, 85.3-100%) and 100% specificity (18/18, 95% CI, 88.6-100%). The IDH mutation in the CSF-tDNA was successfully detected with 100% specificity (95% CI, 87.6-100%) and 73.3% sensitivity (95% CI, 65.6-88.3%). The range of the IDH mutation variant allele frequency (VAF) in the CSF-tDNA was 1.53- 47.9%. 2HG detection in the CSF revealed higher sensitivity (100%) and specificity (100%) in a small subset of patients (n = 7). The D-2HG/L-2HG ratios in IDH-mutant cases varied between 1.2 – 13.8, compared with 0.1 – 0.5 in IDH wild-type gliomas.
Conclusion: Our findings suggest that 2HG spectroscopy and 2HG detection in the CSF are two reliable methods in IDH mutation prediction in gliomas. On the other hand, the sensitivity of genomic IDH mutation detection in the CSF-tDNA was lower when compared with 2HG detection. Further studies are needed to complement the findings of our exploratory analysis.