Approximately one-third of the patients with well-differentiated liposarcoma (WDLPS) will develop a local recurrence. Not much is known about the molecular relationship between the primary tumor and the recurrent tumor, which is important to reveal potential drivers of recurrence. Here we investigated the biology of recurrent WDLPS by comparing paired primary and recurrent WDLPS using microRNA profiling and genome-wide DNA methylation analyses. In total, 27 paired primary and recurrent WDLPS formalin-fixed and paraffin-embedded tumor samples were collected. MicroRNA expression profiles were determined using TaqMan® Low Density Array (TLDA) cards. Genome-wide DNA methylation and differentially methylated regions (DMRs) were assessed by methylated DNA sequencing (MeD-seq). A supervised cluster analysis based on differentially expressed microRNAs between paired primary and recurrent WDLPS did not reveal a clear cluster pattern separating the primary from the recurrent tumors. The clustering was also not based on tumor localization, time to recurrence, age or status of the resection margins. Changes in DNA methylation between primary and recurrent tumors were extremely variable, and no consistent DNA methylation changes were found. As a result, a supervised clustering analysis based on DMRs between primary and recurrent tumors did not show a distinct cluster pattern based on any of the features. Subgroup analysis for tumors localized in the extremity or the retroperitoneum also did not yield a clear distinction between primary and recurrent WDLPS samples. In conclusion, microRNA expression profiles and DNA methylation profiles do not distinguish between primary and recurrent WDLPS and no putative common drivers could be identified.

中文翻译：

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MicroRNA表达和DNA甲基化模式不能区分原发性和复发性高分化脂肪肉瘤。

约有三分之一的高分化脂肪肉瘤（WDLPS）患者会发生局部复发。关于原发性肿瘤和复发性肿瘤之间的分子关系知之甚少，这对于揭示潜在的复发驱动因素很重要。在这里，我们通过使用microRNA分析和全基因组DNA甲基化分析比较配对的初级和复发性WDLPS，研究了复发性WDLPS的生物学特性。总共收集了27对成对的原发性和复发性WDLPS福尔马林固定和石蜡包埋的肿瘤样品。使用TaqMan®低密度阵列（TLDA）卡确定MicroRNA表达谱。通过甲基化DNA测序（MeD-seq）评估全基因组DNA甲基化和差异甲基化区域（DMR）。基于成对的原发性和复发性WDLPS之间差异表达的微小RNA的监督性聚类分析未揭示将原发性和复发性肿瘤区分开的清晰的聚类模式。聚类也不基于肿瘤的位置，复发时间，切除边缘的年龄或状态。原发性和复发性肿瘤之间的DNA甲基化变化极为不同，并且未发现一致的DNA甲基化变化。结果，基于原发性和复发性肿瘤之间DMR的监督聚类分析未显示出基于任何特征的独特聚类模式。对位于四肢或腹膜后部位的肿瘤进行亚组分析也未对原发性和复发性WDLPS样本进行明确区分。结论，