Studies in myeloid neoplasms have described recurrent IDH1 and IDH2 mutations as primarily mutually exclusive. Over a 6-month period of clinical testing with a targeted next-generation sequencing assay, we evaluated 92 patients with acute myeloid leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia and identified a subset of 21 patients (23%) who harbored mutations in either IDH1 or IDH2. Of the 21 patients with IDH mutations, 4 (19%) were found to have single nucleotide variants in both IDH1 and IDH2. An additional patient included in the study was found to have two different IDH2 mutations. The mutations were typically present at different variant allelic frequencies, with one predominating over the other, consistent with the presence of multiple subclones in a single patient. In one case, the variant allelic frequencies in both IDH1 and IDH2 were equally low in the setting of a high percentage of blasts, suggesting that the IDH mutations were unlikely to be present in the founding clone. Given these data, we conclude that dual IDH1/2 mutations likely were previously underestimated, a finding that may carry important treatment implications.
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Supported by T32 training/NIH grant T32 CA 71345-18 (A.M.B.) and Vancouver Coastal Health Research Institute Mentored Clinician Scientist Award, BrainCare BC (S.Y.).
Disclosures: A.T.F. has participated in advisory boards for Agios Pharmaceuticals; Z.Z., L.P.L., and A.J.I. hold patents for the Anchored Multiplex PCR technology, licensed to ArcherDx; Z.Z., L.P.L., and A.J.I. hold stocks in ArcherDx; and L.P.L. and A.J.I. were consultants for Enzymatics, which had acquired ArcherDx.
