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.