The utility of DNA methylation analysis in elderly patients with pilocytic astrocytoma morphology
The utility of DNA methylation analysis in elderly patients with pilocytic astrocytoma morphology
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DOI：
10.1007/s11060-022-04131-3
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发表时间：
2022-09-15
影响因子：
3.9
通讯作者：
Date，Isao
中科院分区：
文献类型：
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作者：
Suruga，Yasuki;Satomi，Kaishi;Date，Isao
目的毛细胞性星形细胞瘤(PA)是一种局限性的低级别星形细胞胶质瘤，一般认为预后良好。然而，PA患者中的一部分显示出不利的结果。方法我们分析了2002年至2021年间来自单一中心的29例经组织学证实的PA患者，并对老年PA患者进行了综合分子分析，因为年龄是预后不良的独立因素。结果确诊时的中位年龄为14岁(3-82岁)，其中4例(14%)为老年患者( ≥ 60岁)。60岁以上患者的无进展存活率和总体存活率较低。我们对4例老年患者中的2例进行了DNA甲基化分析。这两个病例都被组织学诊断为PA，但DNA甲基化分析显示，1例高度恶性星形细胞瘤具有毛发状特征(所有甲基化级别在v11b4和v12.5中均低于0.3)，另一例为胶质母细胞瘤，idh-Wild型(在v11b4和v12.5中均大于0.5)，使用德国癌症研究中心甲基化分析和t-SNE分析显示，在该队列中，具有PA形态的老年患者预后不良。在这些患者中，进一步的分子分析和DNA甲基化分析揭示了高级别星形细胞肿瘤的可能性，包括新定义的实体。
PurposePilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors.MethodsWe analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes.ResultsThe median age at diagnosis was 14 years (range 3–82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis.ConclusionsElderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.