SSX: a multigene family with several members transcribed in normal testis and human cancer

Int J Cancer. 1997 Sep 17;72(6):965-71. doi: 10.1002/(sici)1097-0215(19970917)72:6<965::aid-ijc8>;2-n.


Analysis of t(X;18) translocation in synovial sarcoma had previously led to the definition of the SSX2 gene, the fusion partner on chromosome X. Subsequent screening of testicular cDNA libraries identified 2 highly homologous genes, SSX1 and SSX3. Among these 3 genes, SSX2 has been found to be identical to HOM-MEL-40, which codes for an immunogenic tumor antigen expressed in various human cancers. SSX2 thus belongs to the family of cancer/testis (CT) antigens, i.e., immunogenic protein antigens with characteristic mRNA expression in normal testis and in cancer. To define additional CT antigens, we have immuno-screened a testicular cDNA expression library with an allogeneic serum from a melanoma patient, and both SSX2 and SSX3 were isolated. Further studies using testicular cDNA and SSX probes defined 2 new members of this gene family, SSX4 and SSX5, while a shorter cDNA variant of SSX4 was also identified. All 5 members of the SSX family shared strong sequence homology, with nucleotide homology ranging from 88 to 95% and amino acid homology ranging from 77 to 91%. Genomic cloning of a prototype SSX gene (SSX2) showed that its coding region is encoded by 6 exons, and the shortened form of SSX4 cDNA represents an alternatively spliced product lacking the 5th exon. Analysis of SSX mRNA expression by gene-specific RT-PCR confirmed that all 5 SSX genes are expressed in testis. In addition, analysis of a panel of 12 melanoma cell lines showed strong mRNA expression of either SSX1 (3/12), SSX2 (3/12), SSX4 (1/12), or SSX5 (1/12), indicating variable activation of the genes in malignant cells.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cells, Cultured
  • Chromosomes, Human, Pair 18
  • Exons
  • Gene Library
  • Humans
  • Introns
  • Male
  • Melanocytes
  • Melanoma
  • Molecular Sequence Data
  • Multigene Family*
  • Neoplasm Proteins*
  • Polymerase Chain Reaction
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Testicular Neoplasms / genetics
  • Testicular Neoplasms / metabolism*
  • Testis / metabolism*
  • Transcription, Genetic*
  • Translocation, Genetic
  • Tumor Cells, Cultured
  • X Chromosome


  • Neoplasm Proteins
  • Repressor Proteins
  • synovial sarcoma X breakpoint proteins

Associated data

  • GENBANK/U90840
  • GENBANK/U90841
  • GENBANK/U90842