Intramedullary astrocytomas (IMAs) consist of a heterogeneous group of rare central nervous system (CNS) tumors associated with variable outcomes. A DNA methylation-based classification approach has recently emerged as a powerful tool to further classify CNS tumors. However, no DNA methylation-related studies specifically addressing to IMAs have been performed yet. In the present study, we analyzed 16 IMA samples subjected to morphological and molecular analyses, including DNA methylation profiling. Among the 16 samples, only 3 cases were classified in a reference methylation class (MC) with the recommended calibrated score (≥0.9). The remaining cases were either considered “no-match” cases (calibrated score <0.3, n = 7) or were classified with low calibrated scores (ranging from 0.32 to 0.53, n = 6), including inconsistent classification. To obtain a more comprehensive tool for pathologists, we used different unsupervised analyses of DNA methylation profiles, including our data and those from the Heidelberg reference cohort. Even though our cohort included only 16 cases, hypotheses regarding IMA-specific classification were underlined; a potential specific MC of PA_SPINE was identified and high-grade IMAs, probably consisting of H3K27M wild-type IMAs, were mainly associated with ANA_PA MC. These hypotheses strongly suggest that a specific classification for IMAs has to be investigated.

中文翻译：

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DNA甲基化分析在髓内星形细胞瘤诊断中的作用

髓内星形细胞瘤 (IMA) 由一组异质性的罕见中枢神经系统 (CNS) 肿瘤组成，这些肿瘤与不同的结果相关。最近出现了一种基于 DNA 甲基化的分类方法，作为进一步分类 CNS 肿瘤的有力工具。然而，尚未进行专门针对 IMA 的 DNA 甲基化相关研究。在本研究中，我们分析了 16 个经过形态学和分子分析的 IMA 样本，包括 DNA 甲基化分析。在 16 个样本中，只有 3 个病例被分类为参考甲基化类别 (MC)，推荐的校准分数 (≥0.9)。其余病例要么被认为是“不匹配”病例（校准分数 <0.3，n = 7），要么被分类为低校准分数（范围从 0.32 到 0.53，n = 6），包括不一致的分类。为了为病理学家获得更全面的工具，我们对 DNA 甲基化谱进行了不同的无监督分析，包括我们的数据和来自海德堡参考队列的数据。尽管我们的队列仅包括 16 例病例，但强调了有关 IMA 特定分类的假设；鉴定了 PA_SPINE 的潜在特异性 MC，并且可能由 H3K27M 野生型 IMA 组成的高级 IMA 主要与 ANA_PA MC 相关。这些假设强烈表明必须研究 IMA 的特定分类。鉴定了 PA_SPINE 的潜在特异性 MC，并且可能由 H3K27M 野生型 IMA 组成的高级 IMA 主要与 ANA_PA MC 相关。这些假设强烈表明必须研究 IMA 的特定分类。鉴定了 PA_SPINE 的潜在特异性 MC，并且可能由 H3K27M 野生型 IMA 组成的高级 IMA 主要与 ANA_PA MC 相关。这些假设强烈表明必须研究 IMA 的特定分类。