Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 890-8520, Japan.
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.
Pathol Res Pract. 2024 Nov;263:155598. doi: 10.1016/j.prp.2024.155598. Epub 2024 Sep 28.
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.
先前，我们根据 2021 年世界卫生组织分类系统构建了一个基于 DNA 的下一代测序（NGS）面板，用于胶质瘤的综合诊断。本研究的目的是评估改良的包含 RNA 分析融合基因检测的面板的可行性。使用这种双模 DNA/RNA 面板，我们分析了 210 例胶质瘤和其他病例，以鉴定融合基因，以及基因改变，包括 TERT 启动子（TERTp）突变和 1p/19q 共缺失，在福尔马林固定石蜡包埋组织中。在 210 名患者中，有 35 名患者的肿瘤中检测到融合基因。在 112 例胶质母细胞瘤（GBs）中，有 18 例存在融合基因，包括 EGFR 和 FGFR3 融合。在 IDH 突变星形细胞瘤中，有 6 例存在融合基因，如 MET 和 NTRK2 融合。11 例分子 GBs 和 20 例未分类病例中没有基因融合。其他 11 例肿瘤包括室管膜瘤、毛细胞型星形细胞瘤、弥漫性半球胶质瘤、婴儿型半球胶质瘤和孤立性纤维瘤，表现出诊断性融合基因。总体而言，我们的结果表明，一体式双模 DNA/RNA 面板可靠地检测了与最新 WHO 分类一致的诊断性基因改变。综合病理和分子策略对于脑肿瘤的诊断确认和治疗方案选择可能具有重要价值。
