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

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

doi:10.1016/j.prp.2024.155598

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

Pathol Res Pract. 2024 Sep 28:263:155598. doi: 10.1016/j.prp.2024.155598. Online ahead of print.

Authors

Nayuta Higa¹, Toshiaki Akahane², Mari Kirishima³, Hajime Yonezawa¹, Ryutaro Makino¹, Hiroyuki Uchida¹, Seiya Yokoyama³, Tomoko Takajo¹, Ryosuke Otsuji⁴, Yutaka Fujioka⁴, Yuhei Sangatsuda⁴, Daisuke Kuga⁴, Hitoshi Yamahata¹, Nobuhiro Hata⁵, Nobutaka Horie⁶, Masamichi Kurosaki⁷, Junkoh Yamamoto⁸, Koji Yoshimoto⁴, Akihide Tanimoto⁹, Ryosuke Hanaya¹⁰

Affiliations

¹ Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 890-8520, Japan.
² Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 890-8544, Japan; Center for Human Genome and Gene Analysis, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 890-8544, Japan.
³ Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 890-8544, Japan.
⁴ Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
⁵ Department of Neurosurgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu, Oita 879-5593, Japan.
⁶ Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
⁷ Division of Neurosurgery, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan.
⁸ Department of Neurosurgery, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
⁹ Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 890-8544, Japan; Center for Human Genome and Gene Analysis, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 890-8544, Japan. Electronic address: [email protected].
¹⁰ Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 890-8520, Japan. Electronic address: [email protected].

PMID: 39357189
DOI: 10.1016/j.prp.2024.155598

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.

Keywords: Bimodal DNA/RNA panel; Fusion gene; Glioma; Integrative diagnosis; NGS.