This is a great study that I believe is helping to open a paradigm shift in our understanding of the biology of translocation-associated sarcomas. Related translocation-bearing sarcomas that affect young adults include clear cell sarcoma, extraskeletal myxoid chondrosarcoma, desmoplastic round cell tumor, myxoid liposarcoma and synovial sarcoma. The functions of the fusion oncoproteins in these entitities are not clear, and most research has been directed toward looking for upregulated genes (which are easier to study). We recently published an article about synovial sarcoma which supports the SYT-SSX oncogene as functioning primarily as a transcriptional repressor (Lubieniecka JM et al. Cancer Research June 2008). As in this PLoS ONE paper, effects can be reversed with HDAC inhibitors; TLE is likely also involved. Abnormal transcriptional repression, of tumor supressors and genes driving mesenchymal differentiation, may be fundamental to the biology of the translocation-associated sarcomas.
