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The (Epi)genetics of human synovial sarcoma
Author(s) -
de Bruijn Diederik R. H.,
Nap JanPeter,
van Kessel Ad Geurts
Publication year - 2007
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20399
Subject(s) - synovial sarcoma , epigenetics , biology , fusion protein , chromatin , transcription factor , coactivator , cancer research , chromatin remodeling , gene , activator (genetics) , genetics , microbiology and biotechnology , sarcoma , pathology , medicine , recombinant dna
Human synovial sarcomas are aggressive soft tissue tumors with relatively high rates of recurrences and metastases. They display a variable response to common treatment protocols such as radiation and chemotherapy. For the development of novel diagnostic, prognostic, and therapeutic approaches, detailed information on the molecular mechanisms underlying the development of these tumors is of imperative importance. Fusion of the SS18 and (one of the) SSX genes is a molecular hallmark of human synovial sarcomas. The SS18 and SSX genes encode nuclear proteins that exhibit opposite transcription regulatory activities, likely through epigenetic mechanisms. The SS18 protein functions as a transcriptional coactivator and interacts directly with members of the epigenetic chromatin remodeling and modification machineries. In contrast, the SSX proteins function as transcriptional corepressors and are associated with several Polycomb group proteins. Since the domains involved in these apparently opposite transcription regulatory activities are retained in the SS18–SSX fusion proteins, we hypothesize that these fusion proteins function as “activator–repressors” of transcription. The implications of this model for human synovial sarcoma development and future treatment are discussed. © 2006 Wiley‐Liss, Inc.