Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Anticancer Res. 2022 Apr;42(4):1933-1939. doi: 10.21873/anticanres.15671.
BACKGROUND/AIM: Gliomas are primary malignancies of the central nervous system (CNS). High-grade gliomas are associated with poor prognosis and modest survival rates despite intensive multimodal treatment strategies. Targeting gene fusions is an emerging therapeutic approach for gliomas that allows application of personalized medicine principles. The aim of this study was to identify detectable fusion oncogenes that could serve as predictors of currently available or newly developed targeted therapeutics in cross-sectional samples from glioma patients using next-generation sequencing (NGS).
A total of 637 patients with glial and glioneuronal tumours of the CNS who underwent tumour resection between 2017 and 2020 were enrolled. Detection of fusion transcripts in FFPE tumour tissue was performed by a TruSight Tumour 170 assay and two FusionPlex kits, Solid Tumour and Comprehensive Thyroid and Lung.
Oncogene fusions were identified in 33 patients. The most common fusion was the KIAA1549-BRAF fusion, detected in 13 patients, followed by FGFR fusions (FGFR1-TACC1, FGFR2-CTNNA3, FGFR3-TACC3, FGFR3-CKAP5, FGFR3-AMBRA1), identified in 10 patients. Other oncogene fusions were also infrequently diagnosed, including MET fusions (SRPK2-MET and PTPRZ1-MET) in 2 patients, C11orf95-RELA fusions in 2 patients, EGFR-SEPT14 fusion in 2 patients, and individual cases of SRGAP3-BRAF, RAF1-TRIM2, EWSR1-PALGL1 and TERT-ALK fusions.
The introduction of NGS techniques provides additional information about tumour molecular alterations that can aid the multimodal management of glioma patients. Patients with gliomas positive for particular targetable gene fusions may benefit from experimental therapeutics, enhancing their quality of life and prolonging survival rates.
背景/目的:神经胶质瘤是中枢神经系统(CNS)的原发性恶性肿瘤。尽管采用了强化的多模式治疗策略,高级别神经胶质瘤的预后仍较差,生存率也较低。针对基因融合是神经胶质瘤的一种新兴治疗方法,它允许应用个性化医学原则。本研究的目的是使用下一代测序(NGS)在神经胶质瘤患者的横断面样本中识别可检测的融合致癌基因,这些融合致癌基因可作为目前可用或新开发的靶向治疗的预测因子。
共纳入 2017 年至 2020 年间接受肿瘤切除术的 637 例 CNS 胶质和神经胶质肿瘤患者。通过 TruSight Tumor 170 检测试剂盒和两个 FusionPlex 试剂盒(Solid Tumor 和 Comprehensive Thyroid and Lung)检测 FFPE 肿瘤组织中的融合转录本。
在 33 例患者中发现了致癌基因融合。最常见的融合是 KIAA1549-BRAF 融合,在 13 例患者中检出,其次是 FGFR 融合(FGFR1-TACC1、FGFR2-CTNNA3、FGFR3-TACC3、FGFR3-CKAP5、FGFR3-AMBRA1),在 10 例患者中检出。其他致癌基因融合也很少被诊断,包括 2 例患者的 MET 融合(SRPK2-MET 和 PTPRZ1-MET)、2 例患者的 C11orf95-RELA 融合、2 例患者的 EGFR-SEPT14 融合以及个别病例的 SRGAP3-BRAF、RAF1-TRIM2、EWSR1-PALGL1 和 TERT-ALK 融合。
NGS 技术的引入提供了有关肿瘤分子改变的额外信息,可辅助神经胶质瘤患者的多模式管理。特定可靶向基因融合阳性的神经胶质瘤患者可能受益于实验性治疗,提高其生活质量并延长生存率。