Molecular diagnosis of synovial sarcoma and characterization of a variant SYT-SSX2 fusion transcript

Am J Pathol. 1995 Dec;147(6):1592-9.


The translocation t(X;18)(p11;q11) is seen in > 80% of synovial sarcomas (SS) with informative karyotypes. The breakpoints of the t(X;18) have been cloned and shown to involve two novel genes, SSX (at Xp11) and SYT (at 18q11), which produce a chimeric SYT-SSX transcript as a result of the translocation. Recently, SSX has been shown to be duplicated, with both copies, SSX1 and SSX2, located within distinct subregions of Xp11. We performed a reverse transcriptase polymerase chain reaction (RT-PCR) assay for both chimeric SYT-SSX transcripts in a series of 35 SS (29 monophasic, 6 biphasic) to assess its usefulness in molecular diagnosis and to evaluate the incidence of molecular variants. Of the 35 cases, 29 (83%) showed a specific SYT-SSX RT-PCR product, using a consensus primer for SSX1 and SSX2 Upon excluding three negative cases that had poor quality RNA, the proportion of positives rose to 91% (29/32). The 29 positive cases were further studied using primers specific for either SSX1 or SSX2; 19 cases were positive for SYT-SSX1 and 10 for SYT-SSX2. The relationship of histological subtype (monophasic versus biphasic) to SSX1 or SSX2 involvement was not statistically significant. In a single histologically unremarkable monophasic SS, a slightly larger SYT-SSX2 RT-PCR product was observed. Sequencing of this novel variant showed a 129-bp segment inserted between the usual SYT and SSX2 fusion points, of which 126 bp were derived from a more proximal (5') portion of SSX2 The 3 bp immediately 5' to the fusion point could not be assigned to either SYT or SSX2 and may represent an insertion-deletion or a cryptic splicing event. This fragment maintains the reading frame of the chimeric product and encodes a predicted protein larger by 43 amino acids, which nevertheless replaces the region homologous to the transcriptional repression domain Kruppel-associated box, recently recognized in the 5' portion of the SSX genes, with all but the 3' end of the SYT transcript. Thus, a diagnosis of SS may be confirmed in > 90% of cases using RT-PCR detection of the chimeric transcript resulting from the t(X;18), and the incidence of molecular variants appears low.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Base Sequence
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Proteins / analysis*
  • Neoplasms, Connective Tissue / chemistry*
  • Neoplasms, Connective Tissue / diagnosis
  • Polymerase Chain Reaction
  • Proteins / analysis
  • Proto-Oncogene Proteins
  • RNA, Neoplasm / analysis*
  • RNA, Neoplasm / genetics
  • Recombinant Fusion Proteins / analysis*
  • Repressor Proteins / analysis
  • Sarcoma, Synovial / chemistry*
  • Sarcoma, Synovial / diagnosis
  • Transcription, Genetic*
  • Translocation, Genetic / genetics


  • Neoplasm Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Neoplasm
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • SS18 protein, human
  • synovial sarcoma X breakpoint proteins

Associated data

  • GENBANK/S79894