背景:伴有FGFR3的胶质瘤::TACC3融合主要发生在成人,显示胶质母细胞瘤(GB)的病理特征,通常被归类为胶质母细胞瘤,IDH-野生型。然而,显示低级别胶质瘤(LGG)病理特征的病例导致分类和临床治疗困难。我们报告了一系列8GB和14LGG与FGFR3:TACC3融合,以便更好地表征它们。
方法:集中病理检查,在所有病例中均进行了TERT启动子突变搜索和DNA甲基化分析.通过Kaplan-Meir方法搜索预后因素。
结果:TERT启动子突变记录在所有GB和6/14LGG中。在分类器(v12.5)中甲基化得分>0.9的7例病例中,2被归类为胶质母细胞瘤,4为神经节胶质瘤(GG),1为胚胎发育不良神经上皮肿瘤(DNET)。t-SNE分析显示22例患者分为三组:一组包括12例接近胶质母细胞瘤,IDH-野生型甲基化类别(MC),5例病例均聚集有GG或DNETMC,但无PLNTYMC。无监督聚类分析显示四组,其中两个明显不同:5例年龄相同(<40),LGG的病理特征,缺乏TERT启动子突变,FGFR3(外显子17)::TACC3(外显子10)融合型与LGGMC。相比之下,4例共有年龄(>40岁),胶质母细胞瘤的病理特征,TERT突变了。与较好预后相关的因素是年龄<40岁和缺乏TERT启动子突变。
结论:在FGFR3::TACC3融合的胶质瘤中,年龄,TERT启动子突变,病理特征,DNA甲基化分析和融合亚型是确定患者风险的重要因素。
Gliomas with FGFR3::TACC3 fusion mainly occur in adults, display pathological features of glioblastomas (GB) and are usually classified as glioblastoma, IDH-wildtype. However, cases demonstrating pathological features of low-grade glioma (LGG) lead to difficulties in classification and clinical management. We report a series of 8 GB and 14 LGG with FGFR3:TACC3 fusion in order to better characterize them.
Centralized pathological examination, search for TERT promoter mutation and DNA-methylation profiling were performed in all cases. Search for prognostic factors was done by the Kaplan-Meir method.
TERT promoter mutation was recorded in all GB and 6/14 LGG. Among the 7 cases with a methylation score > 0.9 in the classifier (v12.5), 2 were classified as glioblastoma, 4 as ganglioglioma (GG) and 1 as dysembryoplastic neuroepithelial tumor (DNET). t-SNE analysis showed that the 22 cases clustered into three groups: one included 12 cases close to glioblastoma, IDH-wildtype methylation class (MC), 5 cases each clustered with GG or DNET MC but none with PLNTY MC. Unsupervised clustering analysis revealed four groups, two of them being clearly distinct: 5 cases shared age (< 40), pathological features of LGG, lack of TERT promoter mutation, FGFR3(Exon 17)::TACC3(Exon 10) fusion type and LGG MC. In contrast, 4 cases shared age (> 40), pathological features of glioblastoma, and were TERT-mutated. Relevant factors associated with a better prognosis were age < 40 and lack of TERT promoter mutation.
Among gliomas with FGFR3::TACC3 fusion, age, TERT promoter mutation, pathological features, DNA-methylation profiling and fusion subtype are of interest to determine patients\' risk.