Molecular mechanisms underlying human synovial sarcoma development.
Synovial sarcomas are rather common among soft-tissue tumors, occurring at any age but affecting mainly young adults. The vast majority of synovial sarcomas carries a t(X;18)(p11.2;q11.2) chromosomal translocation, in about one-third of the cases as the sole cytogenetic anomaly. Several studies have indicated that the t(X;18) translocation arises exclusively in synovial sarcomas, therefore being an excellent tool to diagnose this malignancy. The breakpoint-associated genes were recently isolated: SYT, from chromosome 18, and SSX1 and SSX2, both from the X chromosome. This discovery enabled the detection of SYT-SSX fusion transcripts by specific reverse transcriptase-polymerase chain reactions. This molecular genetics methodology has now been applied to numerous tumor samples and has led to the finding that, in contrast to tumors carrying SYT-SSX2 fusions, SYT-SSX1-positive tumors more often exhibit a biphasic histology, show a higher proliferation rate, and are associated with a poorer clinical outcome. It has also been shown that the SYT and SSX proteins are localized in the nucleus, where they appear to play a role in transcriptional regulation, SYT as an activator of transcription and the SSX proteins as transcriptional repressors. It was also found that SYT interacts and colocalizes in the nucleus with the BRM protein, a transcriptional coactivator, and that the SSX proteins colocalize in the nucleus with polycomb group proteins, which are transcriptional corepressors. Together, these studies have provided mechanistic clues about how the SYT-SSX fusion proteins may trigger synovial sarcoma development.
dos Santos
N R
NR
Department of Human Genetics, University Hospital Nijmegen, Nijmegen, The Netherlands.
de Bruijn
D R
DR
van Kessel
A G
AG
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D013584:Sarcoma, Synovial / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics
D015514:Oncogene Proteins, Fusion