All-in-one bimodal DNA and RNA next-generation sequencing panel for integrative diagnosis of glioma.

in Pathology, research and practice by Nayuta Higa, Toshiaki Akahane, Mari Kirishima, Hajime Yonezawa, Ryutaro Makino, Hiroyuki Uchida, Seiya Yokoyama, Tomoko Takajo, Ryosuke Otsuji, Yutaka Fujioka, Yuhei Sangatsuda, Daisuke Kuga, Hitoshi Yamahata, Nobuhiro Hata, Nobutaka Horie, Masamichi Kurosaki, Junkoh Yamamoto, Koji Yoshimoto, Akihide Tanimoto, Ryosuke Hanaya

TLDR

  • The study aims to improve the diagnosis of brain tumors by using a DNA/RNA panel that can detect fusion genes in addition to gene alterations. The panel is reliable for detecting diagnostic gene alterations in accordance with the latest WHO classification. The integrative pathological and molecular strategy could be valuable in confirming the diagnosis and selecting the best treatment options for brain tumors. Future research should focus on improving the sensitivity and specificity of the detection methods and expanding the panel to include more fusion genes.

Abstract

Previously, we constructed a DNA-based next-generation sequencing (NGS) panel for an integrated diagnosis of gliomas according to the 2021 World Health Organization classification system. The aim of the current study was to evaluate the feasibility of a modified panel to include fusion gene detection via RNA-based analysis. Using this bimodal DNA/RNA panel, we analyzed 210 cases of gliomas and others to identify fusion genes in addition to gene alterations, including TERT promoter (TERTp) mutation and 1p/19q co-deletion, in formalin-fixed paraffin-embedded tissues. Of the 210 patients, fusion genes were detected in tumors of 35 patients. Eighteen of 112 glioblastomas (GBs) harbored fusion genes, including EGFR and FGFR3 fusions. In IDH-mutant astrocytoma, 6 of 30 cases showed fusion genes such as MET and NTRK2 fusions. Eleven molecular GBs and 20 not-elsewhere-classified cases harbored no gene fusions. Other 11 tumors including ependymoma, pilocytic astrocytoma, diffuse hemispheric glioma, infant-type hemispheric glioma, and solitary fibrous tumors exhibited diagnostic fusion genes. Overall, our results suggest that the all-in-one bimodal DNA/RNA panel is reliable for detecting diagnostic gene alterations in accordance with the latest WHO classification. The integrative pathological and molecular strategy could be valuable in confirmation of diagnosis and selection of treatment options for brain tumors.

Overview

  • The study aims to evaluate the feasibility of a modified DNA/RNA panel for the detection of fusion genes in addition to gene alterations in gliomas. The panel includes TERTp mutation and 1p/19q co-deletion. The study analyzed 210 cases of gliomas and others to identify fusion genes in formalin-fixed paraffin-embedded tissues. The primary objective is to determine the reliability of the all-in-one bimodal DNA/RNA panel for detecting diagnostic gene alterations in accordance with the latest WHO classification.

Comparative Analysis & Findings

  • Fusion genes were detected in tumors of 35 patients. Eighteen of 112 glioblastomas (GBs) harbored fusion genes, including EGFR and FGFR3 fusions. In IDH-mutant astrocytoma, 6 of 30 cases showed fusion genes such as MET and NTRK2 fusions. Eleven molecular GBs and 20 not-elsewhere-classified cases harbored no gene fusions. Other 11 tumors including ependymoma, pilocytic astrocytoma, diffuse hemispheric glioma, infant-type hemispheric glioma, and solitary fibrous tumors exhibited diagnostic fusion genes. Overall, the results suggest that the all-in-one bimodal DNA/RNA panel is reliable for detecting diagnostic gene alterations in accordance with the latest WHO classification.

Implications and Future Directions

  • The study's findings suggest that the all-in-one bimodal DNA/RNA panel is reliable for detecting diagnostic gene alterations in accordance with the latest WHO classification. The integrative pathological and molecular strategy could be valuable in confirmation of diagnosis and selection of treatment options for brain tumors. Future research should focus on expanding the panel to include more fusion genes and improving the sensitivity and specificity of the detection methods.
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