FUSION OF SYT TO 2 GENES, SSX1 AND SSX2, ENCODING PROTEINS WITH HOMOLOGY TO THE KRUPPELA-ASSOCIATED BOX IN HUMAN SYNOVIAL SARCOMA

We demonstrate that the cytogenetically defined translocation t(X;18)( p11.2;q11.2) found in human synovial sarcoma results in the fusion of the chromosome 18 SYT gene to either of two distinct genes, SSX1 or SS X2, at Xp11.2. The SSX1 and SSX2 genes encode closely related proteins (81% identity) of 188 amino acids that are rich in charged amino acid s. The N-terminal portion of each SSX protein exhibits homology to the Kruppel-associated box (KRAB), a transcriptional repressor domain pre viously found only in Kruppel-type zinc finger proteins. PCR analysis demonstrates the presence of SYT-SSX1 or SYT-SSX2 fusion transcripts i n 29 of 32 of the synovial sarcomas examined, indicating that the dete ction of these hybrid transcripts by PCR may represent a very useful d iagnostic method. Sequence analysis has demonstrated heterogeneity in the fusion transcripts with the formation of two distinct SYT-SSX1 fus ion junctions and two distinct SYT-SSX2 fusion junctions.