Detection of Dual IDH1 and IDH2 Mutations by Targeted Next-Generation Sequencing in Acute Myeloid Leukemia and Myelodysplastic Syndromes

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

12 Scopus Citations
View graph of relations

Author(s)

  • Mia Y. Platt
  • Amir T. Fathi
  • Darrell R. Borger
  • Andrew M. Brunner
  • Robert P. Hasserjian
  • Leonora Balaj
  • Amy Lum
  • Stephen Yip
  • Dora Dias-Santagata
  • Long P. Le
  • Timothy A. Graubert
  • A. John Iafrate
  • Valentina Nardi

Detail(s)

Original languageEnglish
Article number430
Pages (from-to)661-668
Journal / PublicationJournal of Molecular Diagnostics
Volume17
Issue number6
Publication statusPublished - 1 Nov 2015
Externally publishedYes

Abstract

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.

Citation Format(s)

Detection of Dual IDH1 and IDH2 Mutations by Targeted Next-Generation Sequencing in Acute Myeloid Leukemia and Myelodysplastic Syndromes. / Platt, Mia Y.; Fathi, Amir T.; Borger, Darrell R.; Brunner, Andrew M.; Hasserjian, Robert P.; Balaj, Leonora; Lum, Amy; Yip, Stephen; Dias-Santagata, Dora; Zheng, Zongli; Le, Long P.; Graubert, Timothy A.; Iafrate, A. John; Nardi, Valentina.

In: Journal of Molecular Diagnostics, Vol. 17, No. 6, 430, 01.11.2015, p. 661-668.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review