Human Gene Set: ISHIDA_TARGETS_OF_SYT_SSX_FUSIONS

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Standard name ISHIDA_TARGETS_OF_SYT_SSX_FUSIONS
Systematic name M2278
Brief description Genes down-regulated in synovial sarcoma samples with SYT-SSX fusions resulting from translocation of SS18 [GeneSymbol=SS18] to one of the SSX genes.
Full description or abstract Chromosomal translocations are frequently associated with soft-tissue sarcomas. Fusion proteins generated by such translocations often play critical roles in tumorigenesis. Therefore, it is important to understand the function of the fusion protein to develop therapeutic interventions. The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in a fusion between the SYT gene on chromosome 18 and an SSX gene on the X chromosome. Although SYT-SSX fusion proteins appear to trigger synovial sarcoma development, little is known about the downstream targets of SYT-SSX. We found that the SYT-SSX fusion protein produces a dominant-negative function for SYT, which is a transcriptional coactivator. We then analyzed the gene expression profiles of SYT-SSX1-expressing HeLa cells using oligonucleotide microarrays and found that the SYT-SSX1 fusion protein directly down-regulated the expression of COM1, a regulator of cell proliferation. COM1 was found to be expressed at relatively low levels in synovial sarcoma tissues and cell lines. We then investigated the impact of conditional COM1 expression in the synovial sarcoma cell line. Increased COM1 expression resulted in induced apoptosis and in reduced cell growth and colony formation activity. Our results suggested that restoration of COM1 expression may be of therapeutic benefit in synovial sarcoma.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17101797   Authors: Ishida M,Miyamoto M,Naitoh S,Tatsuda D,Hasegawa T,Nemoto T,Yokozeki H,Nishioka K,Matsukage A,Ohki M,Ohta T
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform Human_RefSeq
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Version history 3.1: First introduced

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