Detection of IDH1 Mutations in Plasma Using BEAMing Technology in Patients with Gliomas

SIMPLE SUMMARY: In contrast with other solid tumors, only a few, small studies have shown the feasibility of detecting different biomarkers in the peripheral blood (PB) of patients with gliomas. A prospective study was conducted, enrolling 10 patients with gliomas where 33 consecutive PB samples were analyzed. Among the six patients with isocitrate dehydrogenase 1 (IDH1)-mutant tumors that were surveyed, circulating tumor DNA (ctDNA) was detected in PB in three of them (50%), at timepoints at which the patients were either untreated or exhibited progressive disease. While no false positives were identified, the false-negative rate was high, reaching 86% (18/21). Finally, in one of the IDH1-mutant cases, the Beads, Emulsion, Amplification and Magnetics (BEAMing) digital PCR technology detected one of the two IDH1 mutations that had been detected in the patient’s tumor sample in plasma, 7 years prior to its detection in blood. ABSTRACT: Molecular testing using blood-based liquid biopsy approaches has not been widely investigated in patients with glioma. A prospective single-center study enrolled patients with gliomas ranging from grade II to IV. Peripheral blood (PB) was drawn at different timepoints for circulating tumour DNA (ctDNA) monitoring. Next-generation sequencing (NGS) was used for the study of isocitrate dehydrogenase 1 (IDH1) mutations in the primary tumor. Beads, Emulsion, Amplification and Magnetics (BEAMing) was used for the study of IDH1 mutations in plasma and correlated with the NGS results in the tumor. Between February 2017 and July 2018, ten patients were enrolled, six with IDH1-mutant and four with IDH1 wild-type gliomas. Among the six IDH-mutant gliomas, three had the same IDH1 mutation detected in plasma (50%), and the IDH1-positive ctDNA result was obtained in patients either at diagnosis (no treatment) or during progressive disease. While the false-negative rate reached 86% (18/21), 15 out of the 18 (83%) plasma-negative results were from PB collected from the six IDH-mutant patients at times at which there was no accompanying evidence of tumor progression, as assessed by MRI. There were no false-positive cases in plasma collected from patients with IDH1 wild-type tumors. BEAMing detected IDH1 mutations in the plasma of patients with gliomas, with a modest clinical sensitivity (true positivity rate) but with 100% clinical specificity, with complete agreement between the mutant loci detected in tumor and plasma. Larger prospective studies should be conducted to expand on these findings, and further explore the clearance of mutations in PB from IDH1-positive patients in response to therapy.