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Brain Tumor Pathology

, Volume 35, Issue 2, pp 97–105 | Cite as

A novel high-sensitivity assay to detect a small fraction of mutant IDH1 using droplet digital PCR

  • Masaki Hirano
  • Fumiharu OhkaEmail author
  • Sachi Maeda
  • Lushun Chalise
  • Akane Yamamichi
  • Kosuke Aoki
  • Akira Kato
  • Kuniaki Tanahashi
  • Kazuya Motomura
  • Yusuke Nishimura
  • Masahito Hara
  • Keiko Shinjo
  • Yutaka Kondo
  • Toshihiko Wakabayashi
  • Atsushi Natsume
Original Article

Abstract

Detection of mutations in the isocitrate dehydrogenase 1 (IDH1) gene is useful for accurate diagnosis of lower grade gliomas, as described in the 2016 World Health Organization classification of tumors of the central nervous system. Conventional analysis tools, including Sanger DNA sequencing and immunohistochemistry, might fail to detect a small fraction of mutant IDH1 owing to their limited sensitivity. Considering that lower grade gliomas are infiltrative in nature, a highly sensitive detection assay for IDH1 mutation is required for their accurate diagnosis. In this study, we successfully established a droplet digital PCR (ddPCR) system to detect a small fraction of IDH1 mutation. We could detect 0.05% of mutant IDH1 allele in 30 ng DNA. Using this assay, we could detect a small fraction of mutant IDH1 in a glioma case, identified as a wildtype tumor according to the conventional assays. Additionally, in a small amount of DNA derived from the cerebrospinal fluid, we could detect an IDH1 mutation. In conclusion, the ddPCR system is useful to identify a small fraction of IDH1 mutation in diffuse infiltrative gliomas. This might be useful for precision medicine of these gliomas in the near future and also for the non-invasive diagnosis of these gliomas.

Keywords

Glioma IDH1 mutation Droplet digital PCR 

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Copyright information

© The Japan Society of Brain Tumor Pathology 2018

Authors and Affiliations

  • Masaki Hirano
    • 1
  • Fumiharu Ohka
    • 1
    Email author
  • Sachi Maeda
    • 1
  • Lushun Chalise
    • 1
  • Akane Yamamichi
    • 1
    • 2
    • 3
  • Kosuke Aoki
    • 1
  • Akira Kato
    • 1
  • Kuniaki Tanahashi
    • 1
  • Kazuya Motomura
    • 1
  • Yusuke Nishimura
    • 1
  • Masahito Hara
    • 1
  • Keiko Shinjo
    • 2
  • Yutaka Kondo
    • 2
  • Toshihiko Wakabayashi
    • 1
  • Atsushi Natsume
    • 1
  1. 1.Department of NeurosurgeryNagoya UniversityNagoyaJapan
  2. 2.Division of Cancer BiologyNagoya University Graduate School of MedicineNagoyaJapan
  3. 3.Department of NeurosurgeryMie UniversityTsuJapan

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