Large-scale sequencing led to the identification of driver molecular alterations such as FGFR1 and BRAF in occasional diffuse midline gliomas (DMGs) H3K27-mutant but their significance has not been completely explored. We evaluated these associations in our institutional cohorts. We searched our archives for H3K2M7-mutant gliomas and analyzed the co-occurring genetic alterations. The demographics, clinical information, and pathology were reviewed. Oncoplots and Kaplan-Meier survival curves were generated with the maftools R package. We identified 81 patients (age range 2–68, median 26), of which 79 (97%) were DMGs, and 2 were glioneuronal tumors. The 2 glioneuronal tumors (1 with BRAF fusion and 1 BRAF-V600E-mutant) were removed from the outcome analysis. Four cases had BRAF V600E mutation, 12 had FGFR1 hotspot mutations, and one each had KRAS and NRAS pathogenic mutations. The most common correlating anatomic location was the brainstem for the BRAF group and thalamus for the FGFR1group. Follow-up ranged from 0 to 78 months, average 20.4 months. The overall survival in FGFR1- and BRAF V600E-mutant DMGs was not statistically improved when compared with those that were wildtype. However, the possibility of targeted therapy argues for comprehensive sequencing of H3K27-altered gliomas.

中文翻译：

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H3K27 改变的弥漫性中线胶质瘤伴 MAPK 通路改变：预后和治疗意义

大规模测序导致在偶尔发生弥漫性中线神经胶质瘤 (DMG) H3K27 突变的驱动分子改变（例如 FGFR1 和 BRAF）的鉴定，但其重要性尚未得到完全探索。我们在我们的机构群体中评估了这些关联。我们搜索了 H3K2M7 突变神经胶质瘤的档案并分析了同时发生的基因改变。回顾了人口统计学、临床信息和病理学。Oncoplots 和 Kaplan-Meier 生存曲线是使用 maftools R 软件包生成的。我们确定了 81 名患者（年龄范围 2-68 岁，中位数 26），其中 79 名 (97%) 是 DMG，2 名是胶质神经元肿瘤。2 个胶质神经元肿瘤（1 个具有 BRAF 融合和 1 个 BRAF-V600E 突变）从结果分析中删除。4例有BRAF V600E突变，12例有FGFR1热点突变，1例有KRAS和NRAS致病性突变。最常见的相关解剖位置是 BRAF 组的脑干和 FGFR1 组的​​丘脑。随访0～78个月，平均20.4个月。与野生型相比，FGFR1 和 BRAF V600E 突变 DMG 的总体存活率没有统计学上的改善。然而，靶向治疗的可能性主张对 H3K27 改变的神经胶质瘤进行全面测序。