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

癌症睾丸抗原 1b/a 到肉瘤通路的系统水平映射鉴定出活化的 Ran 结合-2 E3 SUMO 蛋白连接酶和传导蛋白样增强子蛋白 1

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作者:Nikolaos A Papanikolaou, Prodromos Hytiroglou, Pavlina Pantelidou, Athanasios G Papavassiliou, Lloyd L Old

Abstract

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.

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