Expression data from 87 complex sarcomas

Based on the transcriptome analysis of 555 sarcomas, we identified a group of tightly clustered leiomyosarcomas (LMS) due to their gene expression homogeneity. We named them “hLMS” and the other LMS “oLMS”. We derived a transcriptional signature able to identify each group and used it to classify patients from two independent cohorts. In all cohorts, hLMS were preferentially carried by women, located in the internal trunk, highly differentiated, and similarly altered at the genomic level. Based on integrative bioinformatic analysis, we show that hLMS originate from vascular smooth muscle cells presenting both contractile and synthetic characteristics, while oLMS could derive from fibroblasts. We found strong MYOCD expression to be an hLMS-specific driver and show that the MYOCD/SRF axis is essential only for hLMS survival. Identification of hLMS could become standard clinical practice, leading to the development of specific effective treatments with MYOCD/SRF inhibitors. These 87 samples from leiomyosarcoma primary tumors were analysed on Affymetrix and Agilent platforms and both datasets were used to define genes with consistent expression between the platforms. These genes were then selected in other datasets from the two plaforms before combination and normalization. 87 Complex Sarcomas hybridized to Agilent-014850 Whole Human Genome Microarray 4x44K G4112F

基于对555例肉瘤的转录组分析，我们基于基因表达均一性特征，鉴定出一组紧密聚类的平滑肌肉瘤（leiomyosarcoma，LMS），将其命名为"hLMS"，其余LMS则命名为"oLMS"。我们构建了可区分两类肿瘤的转录特征，并以此对两个独立队列的患者进行分类。在所有分析队列中，hLMS均好发于女性，肿瘤多位于躯干内部，且呈高度分化状态，基因组层面的改变模式高度相似。通过整合生物信息学分析，我们证实hLMS起源于同时具备收缩与合成功能特性的血管平滑肌细胞，而oLMS则可能源自成纤维细胞。我们发现MYOCD基因的高表达是hLMS特异性的驱动因素，并证实MYOCD/SRF信号轴仅对hLMS的存活至关重要。hLMS的鉴定有望成为临床常规检测手段，进而推动基于MYOCD/SRF抑制剂的特异性有效治疗方案的开发。本研究针对87例原发性平滑肌肉瘤样本，采用Affymetrix与Agilent平台开展转录组分析，并利用两类数据集筛选出在两种平台上表达一致性良好的基因。随后，我们在来自上述两个平台的其他数据集内对这些基因进行筛选，再进行合并与标准化处理。另有87例复杂性肉瘤样本采用Agilent-014850全人类基因组微阵列4x44K G4112F完成杂交检测。