Table1_Systems-Level Mapping of Cancer Testis Antigen 1b/a to Sarcoma Pathways Identifies Activated Ran Binding-2 E3 SUMO-Protein Ligase and Transducin-Like Enhancer Protein 1.XLS

Here we describe the identification of genes and their encoded proteins that are expressed in advanced grade tumors by reconstruction of a sarcoma cancer testis gene 1b/a (catg1b/a) network. CTAG1B/A is an ortholog of the yeast/Drosophila transcription factor Pcc1p, and a member of the KEOPS transcription complex. It has been implicated in telomere maintenance and transcriptional regulation through association with chromatin remodeling factors and is only expressed during adult testis germ cell differentiation. Ctag1b/a is re-activated in synovial sarcomas and myxoid liposarcomas but not in differentiated liposarcomas. We mapped CTAG1B/A protein to sarcoma transcription pathways with gene set expression analysis (GSEA) and using independent samples, we immunohistochemically identified expression of at least two network neighbors, RANBP2, and TLE1, thus validating our approach. This work demonstrates that mapping unknown genes to functional pathways by network re-construction is a powerful tool that can be used to identify candidate oncoproteins.

在本研究中，我们详细描述了通过重建肉瘤癌睾丸基因1b/a（catg1b/a）网络，识别在高级别肿瘤中表达的基因及其编码的蛋白质。CTAG1B/A为酵母/果蝇转录因子Pcc1p的直系同源物，并且是KEOPS转录复合体的一员。该基因与染色质重塑因子相互作用，参与端粒维护和转录调控，仅在成年睾丸生殖细胞分化过程中表达。Ctag1b/a在滑膜肉瘤和粘液样脂肪肉瘤中被重新激活，但在分化脂肪肉瘤中则不表达。我们利用基因集表达分析（GSEA）将CTAG1B/A蛋白映射到肉瘤转录通路，并使用独立样本通过免疫组化方法鉴定至少两个网络邻近基因RANBP2和TLE1的表达，从而验证了我们的方法。本研究证明，通过网络重建将未知基因映射到功能通路是一种强大的工具，可用于识别候选癌蛋白。