ANALYSIS OF ABNORMAL GENES ASSOCIATED WITH SYNOVIAL SARCOMA ONCOGENESIS.

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Chromosome translocation t (X ; 18)(p11.2 ; q11.2) has been detected in more than 95% of the synovial sarcomas. The proximal portion of the SYT gene at 18q11 is fused the distal portion of one of two duplicated genes atXp11, SSX1 and SSX2. This SYT-SSX chimeric gene is considered to be closely associated with synovial sarcoma oncogenesis. Detection of this chimeric gene is useful in pathological diagnosis of synovial sarcoma. We extracted RNA from routinely-processed cytological and histological specimens of synovial sarcoma cases and detected SYT-SSX chimeric transcript in more than 90% of the cases using highly sensitive RT-PCR.In the next step, we studied the clinicopathological significance of the SSX type involved in the SYT-SSX fusion. Synovial sarcoma cases that had no distant metastasis at surgery were included. The SSX type involved in each case was confirmed, then, histological type, mitotic figures, prognosis, and expression of following proteins were investigated ; cell cycle-associated proteins, Ki67 and p27, and apoptosis-associated proteins, p53 and bcl-2. SYT-SSX1 fusion was associated with high expression of Ki67 and increased mitotic figures, but not with other factors. Clinically, SYT-SSX1, mitotic figures, and Ki67 expression were important factors for worse disease-free survival. We are interested in the mechanism by which SYT-SSX fusion proteins promote cell proliferation. Bacause SYT-SSX fusion protein does not possess apparent DNA-or RNA-binding domains, the fusion protein may bind to unknown proteins that would regulate cell cycling. We have found some candidate proteins by Two-hybrid system using SYT-SSX fusion gene transfection into yeast, and are studying the significance of these proteins in synovial sarcoma oncogenesis.