The molecular biology of ependymomas is not well understood and this is particularly true for ependymoma relapses. We aimed at finding out if and to which extent, relapses differ from their corresponding primary tumors on the morphological, chromosomal and epigenetic level. We investigated 24 matched ependymoma primary and relapsed tumor samples and, as a first step, compared cell density, necrosis, vessel proliferation, Ki67 proliferative index, trimethylation at H3K27 and expression of CXorf67. For the investigation of global methylation profiles, we used public data in order to analyze copy number variation profiles, differential methylation, methylation status and fractions of hypo‐ and hypermethylated CpGs in different epigenomic substructures. Morphologically, we found a significant increase with relapse in cell density and proliferation. H3K27 trimethylation and CXorf67 expression remained stable between primary and relapse tumor samples, and the analysis of DNA methylation profiles neither revealed significant differences in copy number variations nor differentially methylated regions. Significant differences in the methylation status were found for CpG islands, but also in N Shelves or S Shelves, depending on the molecular subgroup. The fraction of probes changing their methylation in the epigenomic substructures appeared subgroup‐specific. Most changes occur in CpG islands, for which relapsed tumors demonstrate higher methylation values than primary tumors. The morphological differences reflect increased aggressiveness upon ependymoma relapse, but, despite slight changes, this observation does not appear to be sufficiently explained by epigenetic changes.

中文翻译：

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室管膜瘤复发伴随着相对稳定的表观基因组，但肿瘤形态发生了严重改变

室管膜瘤的分子生物学尚不清楚，对于室管膜瘤复发尤其如此。我们旨在找出复发是否以及在多大程度上与其相应的原发性肿瘤在形态、染色体和表观遗传水平上有所不同。我们研究了 24 个匹配的室管膜瘤原发和复发肿瘤样本，作为第一步，比较了细胞密度、坏死、血管增殖、Ki67 增殖指数、H3K27 的三甲基化和 CXorf67 的表达。为了研究全局甲基化谱，我们使用公共数据来分析拷贝数变异谱、差异甲基化、甲基化状态以及不同表观基因组亚结构中低甲基化和高甲基化 CpG 的分数。在形态学上，我们发现随着细胞密度和增殖的复发而显着增加。H3K27 三甲基化和 CXorf67 表达在原发性和复发性肿瘤样本之间保持稳定，DNA 甲基化谱的分析既未显示拷贝数变异的显着差异，也未显示甲基化区域的显着差异。发现 CpG 岛的甲基化状态存在显着差异，但在 N 搁架或 S 搁架中也存在显着差异，这取决于分子亚群。在表观基因组亚结构中改变其甲基化的探针部分出现亚组特异性。大多数变化发生在 CpG 岛中，复发肿瘤表现出比原发肿瘤更高的甲基化值。形态学差异反映了室管膜瘤复发时的侵袭性增加，但是，尽管有轻微的变化，但表观遗传变化似乎不能充分解释这一观察结果。