Molecular diagnosis of diffuse glioma using a chip-based digital PCR system to analyze IDH, TERT, and H3 mutations in the cerebrospinal fluid

Yutaka Fujioka, Nobuhiro Hata, Yojiro Akagi, Daisuke Kuga, Ryusuke Hatae, Yuhei Sangatsuda, Yuhei Michiwaki, Takeo Amemiya, Kosuke Takigawa, Yusuke Funakoshi, Aki Sako, Toru Iwaki, Koji Iihara, Masahiro Mizoguchi

研究成果: Contribution to journalArticle査読

2 被引用数 (Scopus)

抄録

Purpose: Conventional genetic analyzers require surgically obtained tumor tissues to confirm the molecular diagnosis of diffuse glioma. Recent technical breakthroughs have enabled increased utilization of cell-free tumor DNA (ctDNA) in body fluids as a reliable resource for molecular diagnosis in various cancers. Here, we tested the application of a chip-based digital PCR system for the less invasive diagnosis (i.e., liquid biopsy) of diffuse glioma using the cerebrospinal fluid (CSF). Methods: CSF samples from 34 patients with diffuse glioma were collected from the surgical field during craniotomy. Preoperative lumbar CSF collection was also performed in 11 patients. Extracted ctDNA was used to analyze diagnostic point mutations in IDH1 R132H, TERT promoter (C228T and C250T), and H3F3A (K27M) on the QuantStudio® 3D Digital PCR System. These results were compared with their corresponding tumor DNA samples. Results: We detected either of the diagnostic mutations in tumor DNA samples from 28 of 34 patients. Among them, we achieved precise molecular diagnoses using intracranial CSF in 20 (71%). Univariate analyses revealed that the World Health Organization (WHO) grade (p = 0.0034), radiographic enhancement (p = 0.0006), and Mib1 index (p = 0.01) were significant predictors of precise CSF-based molecular diagnosis. We precisely diagnosed WHO grade III or IV diffuse gliomas using lumbar CSF obtained from 6 (87%) of 7 patients with tumors harboring any mutation. Conclusion: We established a novel, non-invasive molecular diagnostic method using a chip-based digital PCR system targeting ctDNA derived from CSF with high sensitivity and specificity, especially for high-grade gliomas.

本文言語英語
ページ(範囲)47-54
ページ数8
ジャーナルJournal of Neuro-Oncology
152
1
DOI
出版ステータス出版済み - 3 2021
外部発表はい

All Science Journal Classification (ASJC) codes

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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