Intramedullary astrocytomas (IMAs) are rare tumors, and few studies specific to the molecular alterations of IMAs have been performed. Recently, KIAA1549-BRAF fusions and the H3F3A p.K27M mutation have been described in low-grade (LG) and high-grade (HG) IMAs, respectively. In the present study, we collected clinico-radiological data and performed targeted next-generation sequencing for 61 IMAs (26 grade I pilocytic, 17 grade II diffuse, 3 LG, 3 grade III and 12 grade IV) to identify KIAA1549-BRAF fusions and mutations in 33 genes commonly implicated in gliomas and the 1p/19q regions. One hundred seventeen brain astrocytomas were analyzed for comparison. While we did not observe a difference in clinico-radiological features between LG and HG IMAs, we observed significantly different overall survival (OS) and event-free survival (EFS). Multivariate analysis showed that the tumor grade was associated with better OS while EFS was strongly impacted by tumor grade and surgery, with higher rates of disease progression in cases in which only biopsy could be performed. For LG IMAs, EFS was only impacted by surgery and not by grade. The most common mutations found in IMAs involved TP53, H3F3A p.K27M and ATRX. As in the brain, grade I pilocytic IMAs frequently harbored KIAA1549-BRAF fusions but with different fusion types. Non-canonical IDH mutations were observed in only 2 grade II diffuse IMAs. No EGFR or TERT promoter alterations were found in IDH wild-type grade II diffuse IMAs. These latter tumors seem to have a good prognosis, and only 2 cases underwent anaplastic evolution. All of the HG IMAs presented at least one molecular alteration, with the most frequent one being the H3F3A p.K27M mutation. The H3F3A p.K27M mutation showed significant associations with OS and EFS after multivariate analysis. This study emphasizes that IMAs have distinct clinico-radiological, natural evolution and molecular landscapes from brain astrocytomas.

中文翻译：

---

髓内星形细胞瘤的临床，放射学和分子表征。

髓内星形细胞瘤（IMA）是一种罕见的肿瘤，很少有针对IMA分子改变的研究。最近，分别在低级（LG）和高级（HG）IMA中描述了KIAA1549-BRAF融合和H3F3A p.K27M突变。在本研究中，我们收集了临床放射学数据，并对61个IMA（26个I级毛细胞，17个II级弥漫性，3个LG，3个III级和12个IV级）进行了靶向的下一代测序，以识别KIAA1549-BRAF融合蛋白和通常与神经胶质瘤和1p / 19q区域有关的33个基因的突变。分析了117个脑星形细胞瘤以进行比较。虽然我们没有观察到LG和HG IMA在临床放射学特征上存在差异，但我们观察到总体生存期（OS）和无事件生存期（EFS）明显不同。多变量分析显示，肿瘤分级与更好的OS相关，而EFS受肿瘤分级和手术的强烈影响，在仅需进行活检的情况下，疾病进展速度更高。对于LG IMA，EFS仅受手术影响，而不受等级影响。在IMA中发现的最常见的突变涉及TP53，H3F3A p.K27M和ATRX。就像在大脑中一样，I级毛细胞IMA经常带有KIAA1549-BRAF融合，但融合类型不同。仅在2个II级弥散IMA中观察到非经典IDH突变。在IDH野生型II级弥散IMA中未发现EGFR或TERT启动子改变。后面这些肿瘤似乎预后良好，仅2例发生了间变性进化。所有HG IMA都至少发生了一种分子改变，其中最常见的是H3F3A p.K27M突变。多变量分析后，H3F3A p.K27M突变与OS和EFS显着相关。这项研究强调，IMA具有与脑星形细胞瘤不同的临床放射学，自然进化和分子景观。