Due to the rare incidence of spinal cord astrocytomas, their molecular features remain unclear. Here, we characterized the landscapes of mutations in H3 K27M, isocitrate dehydrogenase 1 (IDH1) R132H, BRAF V600E, and the TERT promoter in 83 diffuse spinal cord astrocytic tumors. Among these samples, thirty-five patients had the H3 K27M mutation; this mutant could be observed in histological grade II (40%), III (40%), and IV (20%) astrocytomas. IDH1 mutations were absent in 58 of 58 cases tested. The BRAF V600E mutation (7/57) was only observed in H3-wildtype astrocytomas, and was associated with a better prognosis in all histological grade II/III astrocytomas. TERT promoter mutations were observed in both H3 K27M-mutant (4/25) and -wildtype (9/33) astrocytomas, and were associated with a poor prognosis in H3-wildtype histological grade II/III astrocytomas. In the 2016 WHO classification of CNS tumors, H3 K27M-mutant diffuse midline gliomas, including spinal cord astrocytomas, are categorized as WHO grade IV. Here, we noticed that the median overall survival of histological grade II/III H3 K27M-mutant cases (n = 28) was significantly longer than that of either the total histological grade IV cases (n = 12) or the H3 K27M-mutant histological grade IV cases (n = 7). We also directly compared H3 K27M-mutant astrocytomas to H3-wildtype astrocytomas of the same histological grade. In histological grade II astrocytomas, compared to H3-wildtype cases (n = 37), H3 K27M-mutant patients (n = 14) had showed a significantly higher Ki-67-positive rate and poorer survival rate. However, no significant differences in these parameters were observed in histological grade III and IV astrocytoma patients. In conclusion, these findings indicate that spinal cord astrocytomas are considerably different from hemispheric and brainstem astrocytomas in terms of their molecular profiles, and that the histological grade cannot be ignored when assessing the prognosis of H3 K27M-mutant spinal cord astrocytomas.

中文翻译：

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有或没有H3 K27M突变的脊髓神经胶质瘤的分子特征。

由于脊髓星形细胞瘤的罕有发生，其分子特征仍不清楚。在这里，我们表征了83个弥漫性脊髓星形细胞肿瘤中H3 K27M，异柠檬酸脱氢酶1（IDH1）R132H，BRAF V600E和TERT启动子的突变情况。在这些样本中，有35名患者发生了H3 K27M突变；可以在组织学II级（40％），III级（40％）和IV级（20％）星形细胞瘤中观察到该突变体。测试的58例病例中有58例没有IDH1突变。仅在H3野生型星形细胞瘤中观察到了BRAF V600E突变（7/57），并且在所有组织学II / III级星形星形细胞瘤中预后较好。在H3 K27M突变（4/25）和-野生型（9/33）星形细胞瘤中均观察到TERT启动子突变，并与H3野生型组织学II / III级星形细胞瘤预后不良有关。在2016年WHO对CNS肿瘤的分类中，H3 K27M突变型弥漫性中线神经胶质瘤（包括脊髓星形细胞瘤）被归类为WHO IV级。在这里，我们注意到组织学II / III级H3 K27M突变病例（n = 28）的中位总生存期明显长于组织学IV级总病例（n = 12）或H3 K27M突变组织学的平均存活期。 IV级病例（n = 7）。我们还直接比较了H3 K27M突变星形细胞瘤与相同组织学等级的H3野生型星形细胞瘤。在组织学II级星形细胞瘤中，与H3野生型病例（n = 37）相比，H3 K27M突变患者（n = 14）表现出明显更高的Ki-67阳性率和较差的存活率。然而，在组织学III级和IV级星形细胞瘤患者中未观察到这些参数的显着差异。总之，这些发现表明，脊髓星形细胞瘤的分子谱与半球和脑干星形细胞瘤有很大不同，并且在评估H3 K27M突变型脊髓星形细胞瘤的预后时，组织学等级不可忽视。