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Abstract
Objective: The IDH1R132H mutation is both a strong prognostic predictor and a diagnostic hallmark of gliomas and therefore has major clinical relevance. Here, we developed a new technique to detect the IDH1R132H mutation in the plasma of patients with glioma.
Methods: Small-size DNA (150–250 base pairs) was extracted from the plasma of 31 controls and 80 patients with glioma with known IDH1R132H status and correlated with MRI data. The IDH1R132H mutation was detected by a combination of coamplification at lower denaturation temperature and digital PCR.
Results: The small size DNA concentration was 1.2 ng/mL (range 0.1–6.6) in controls vs 1.2 ng/mL (range 0.1–50.3) in patients with glioma (p = not significant) and 0.9 ng/mL (0.0–3.0) in low-grade gliomas vs 1.5 ng/mL in high-grade gliomas (p < 0.01). The small size DNA concentration correlated with enhancing tumor volume (1.6 ng/mL [0.4–24.9] when <10 cm3 and 14.0 ng/mL [0.6–50.3] when ≥10 cm3). The IDH1R132H mutation was detected in 15 out of 25 plasma DNA mixtures (60%) from patients with mutated tumors and in none of the 14 patients with a nonmutated tumor. The sensitivity increased with enhancing tumor volume (3/9 in nonenhancing tumors, 6/10 for enhancing volume <10 cm3, and 6/6 for enhancing volume ≥10 cm3).
Conclusion: With a specificity of 100% and a sensitivity related to the tumor volume and contrast enhancement, IDH1R132H identification has a valuable diagnostic accuracy in patients not amenable to biopsy.
GLOSSARY
- BBB=
- blood–brain barrier;
- bp=
- base pair;
- COLD PCR=
- coamplification at lower denaturation temperature PCR;
- EDTA=
- ethylene diamine tetraacetic acid;
- FLAIR=
- fluid-attenuated inversion recovery;
- HC=
- healthy control;
- HGG=
- WHO high-grade gliomas;
- IDH1=
- isocitrate dehydrogenase 1;
- LGG=
- WHO low-grade gliomas;
- LNA=
- locked nucleic acid;
- LOH=
- loss of heterozygosity;
- NS=
- nonsignificant;
- ROC=
- receiver operating characteristic
Footnotes
Study funding: Supported by grants from the Association pour la Recherche sur le Cancer and the Cancéropole Ile de France.
Supplemental data at www.neurology.org
- Received February 26, 2012.
- Accepted May 29, 2012.
- Copyright © 2012 by AAN Enterprises, Inc.
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