SSX: a multigene family with several members transcribed in normal testis and human cancer.
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.
Gure
A O
AO
Ludwig Institute for Cancer Research, New York Branch, Memorial Sloan-Kettering Cancer Center, New York, USA.
Türeci
O
O
Sahin
U
U
Tsang
S
S
Scanlan
M J
MJ
Jäger
E
E
Knuth
A
A
Pfreundschuh
M
M
Old
L J
LJ
Chen
Y T
YT
D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D002887:Chromosomes, Human, Pair 18; D005091:Exons; D015723:Gene Library; D006801:Humans; D007438:Introns; D008297:Male; D008544:Melanocytes; D008545:Melanoma; D008969:Molecular Sequence Data; D005810:Multigene Family; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D014960:X Chromosome
D009363:Neoplasm Proteins; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins