Expression profiles of Ewing family of tumors authenticate distinct molecular entities. Homo sapiens

The concept of Ewing family of tumors (EFT), characterized by FET-ETS fusions, has been recently challenged by the description of Ewing-like tumors with different gene fusions. Here we investigate the similarities and differences of FET-ETS, BCOR-CCNB3, CIC-DUX4 and EWSR1-NFATc2 tumors samples with a number of other sarcomas. Unsupervised clustering of gene expression profiles fully discriminates these four molecular entities. Specific gene signatures and pathways were further validated in model cell lines. While a clear inflammatory signature characterizes EWSR1-NFATc2 tumors, BCOR-CCNB3 and CIC-DUX4 exhibit high expression of homeobox and ETS protein families, respectively. We strongly suggest that abnormalities of chromatin remodeling may gather CIC-DUX4 and BCOR-CCNB3 tumors with rhabdoid tumors and synovial sarcomas. Overall design: This dataset conains 14 CIC-DUX4 and 7 EWSR1-NFATc2 tumor samples as well as Human mesenchymal cell line expressing EWSR1-NFATc2 (duplicates) or mock treated (duplicates) and IB120 CIC-DUX4 cell line expressing an shRNA directed against CIC-DUX4 (4 replicates) or mock treated (duplicates).

以FET-ETS融合为特征的尤文肉瘤家族（Ewing family of tumors, EFT）的概念，近期被携带不同基因融合的尤文样肿瘤的报道所挑战。本研究针对FET-ETS、BCOR-CCNB3、CIC-DUX4及EWSR1-NFATc2肿瘤样本与其他多种肉瘤的异同展开系统探究。对基因表达谱开展无监督聚类分析，可完全区分这四种分子亚型。研究进一步在模型细胞系中验证了特异性基因特征与通路：EWSR1-NFATc2肿瘤具有典型的炎症特征，而BCOR-CCNB3与CIC-DUX4肿瘤则分别高表达同源盒（homeobox）蛋白家族与ETS蛋白家族。我们推测，染色质重塑异常可能将CIC-DUX4、BCOR-CCNB3肿瘤与横纹肌样瘤、滑膜肉瘤归为同一类群。
总体实验设计：本数据集包含14例CIC-DUX4肿瘤样本、7例EWSR1-NFATc2肿瘤样本；此外还包含两类工程化细胞系：一是分别过表达EWSR1-NFATc2（设置2个生物学重复）或mock处理（空载对照，设置2个生物学重复）的人间充质细胞系，二是携带靶向CIC-DUX4的短发夹RNA（short hairpin RNA, shRNA）（设置4个生物学重复）或mock处理（空载对照，设置2个生物学重复）的IB120 CIC-DUX4细胞系。