Isocitrate dehydrogenase (IDH) variants can lead to the development and/or progression of various solid tumors and hematological malignancies. IDH testing can guide diagnosis, prognosis, and therapeutic choice and typically relies on NGS, IHC, or PCR-based assays. Here, we evaluated the analytical performance of the Idylla IDH1-2 mutation assay for IDH variant detection using 70 fixed samples from patients with solid tumors and 36 DNA extracts from patients with acute myeloid leukemias previously characterized by NGS +/− IHC. Idylla IDH1-2 mutation assay gave 98.1% of valid results with an overall agreement, sensitivity, and specificity of 97.1%, 96.2%, and 98.1%, respectively, compared to NGS. Using commercial DNA standards, the limit of detection of the assay was 1.6% and 0.5% for IDH1 R132H and IDH2 R172K variants, respectively. Based on these data, the Idylla IDH1-2 mutation assay represents a fast and reliable alternative to detect IDH hotspot variants in solid tumors and hematological malignancies using either fixed tissue sections or DNA extracts. Particular attention, however, is needed for the interpretation of cases with cycle of quantification values of the internal controls over 35, for which a variant with low allelic frequency could be missed due to low DNA quantity or quality.
Gilson et al. (2026) studied this question.