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Targeted next-generation sequencing panel (TruSight Tumor 170) in diffuse glioma: a single institutional experience of 135 cases

  • Kiyong Na
  • Hyun-Soo Kim
  • Hyo Sup Shim
  • Jong Hee Chang
  • Seok-Gu Kang
  • Se Hoon KimEmail author
Clinical Study

Abstract

Purpose

The TruSight Tumor 170 (TST-170) panel consists of a DNA workflow for the identification of single-nucleotide variants, small insertions and deletions, and copy number variation, as well as a panel of 55 genes for a RNA workflow for the identification of splice variants and gene fusions. To date, the application of TST-170 in diffuse gliomas (DGs) has not been described.

Methods

We analyzed 135 samples of DG, which were diagnosed by WHO criteria based on histological features and conventional molecular tests including immunostaining, 1p/19q FISH, and analysis of MGMT methylation and TERT promoter mutation.

Results

A total of 135 cases consisted of 38 IDH-mutant [17 astrocytoma (AC), 13 oligodendroglioma (OD) and eight glioblastoma (GBM)], 87 IDH-wildtype (six AC, three OD and 78 GBM), and 10 diffuse midline glioma, H3K27M-mutant. DNA analysis enabled the detection of all mutations identified in these samples by conventional techniques, and the results were highly comparable to the known mutations in each subtype. RNA analysis detected four fusion genes including PTPRZ1MET, FGFR3TACC3, FAM131BBRAF, and RETCCDC6 and one splicing variant (EGFR vIII mutant). Clustered copy number loss in 1p and 19q loci genes were detected in 1p/19q-codeleted OD.

Conclusions

The application of TST-170 panel based NGS in clinical and laboratory setting is expected to improve diagnostic accuracy and prognostication. Most benefits are expected in IDH-wildtype DG, a group of genetically heterogenous tumors harboring DNA sequence changes, copy number alterations, and fusions in a large number of oncogenes and tumor suppressor genes.

Keywords

Glioma Next-generation sequencing TST-170 Molecular profiles 

Notes

Funding

This work was supported by the Brain Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning (Grant No. 2016M3C7A1913844).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11060_2019_3114_MOESM1_ESM.docx (22 kb)
Supplementary file 1 (DOCX 21 KB)
11060_2019_3114_MOESM2_ESM.docx (37 kb)
Supplementary file 2 (DOCX 37 KB)
11060_2019_3114_MOESM3_ESM.xlsx (24 kb)
Supplementary file 3 (XLSX 24 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PathologyKyung Hee University School of MedicineSeoulRepublic of Korea
  2. 2.Department of PathologyYonsei University College of Medicine, Severance HospitalSeoulRepublic of Korea
  3. 3.Department of NeurosurgeryYonsei University College of Medicine, Severance HospitalSeoulRepublic of Korea

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