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

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.

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.

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 PTPRZ1-MET, FGFR3-TACC3, FAM131B-BRAF, and RET-CCDC6 and one splicing variant (EGFR vIII mutant). Clustered copy number loss in 1p and 19q loci genes were detected in 1p/19q-codeleted OD.

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.