Disease relevance of SSX1

• Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma [1].
• SSX cancer testis antigens are expressed in most multiple myeloma patients: co-expression of SSX1, 2, 4, and 5 correlates with adverse prognosis and high frequencies of SSX-positive PCs [2].
• To determine the reason for this discrepancy, we analyzed cDNA from HS-SY-3 cells, as well as the original sarcoma tissue by the rapid amplification of cDNA 3' end assay, and found that the chimaeric cDNA was 240 bp shorter than the previously established SYT/SSX1 cDNA due to truncation of the 3' side of SSX1 [3].
• Furthermore, the established RT-PCR protocol was used to evaluate the feasibility of SYT-SSX1/2 fusion transcript detection for minimal residual disease analysis [4].
• Prompted by the frequent detection of SSX1 in a previous comprehensive expression profile of the Hodgkin's lymphoma (HL) cell line L428, we analyzed SSX expression by nonnested reverse-transcription polymerase chain reaction (RT-PCR) in 4 HL cell lines (L428, L540, HD-MY-Z, and KM-H2) and 32 tumor samples of HL [5].

High impact information on SSX1

• 2. The SSX1 and SSX2 genes encode closely related proteins (81% identity) of 188 amino acids that are rich in charged amino acids [1].
• 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 SSX2, at Xp11 [1].
• A subset of synovial sarcoma, predominantly cases with the SYT-SSX1 fusion, shows foci of morphologic epithelial differentiation in the form of nests of glandular epithelium [6].
• The translocation results in fusion of the SYT gene on chromosome 18 to either the SSX1 or the SSX2 gene, two homologous genes within Xp11 [7].
• IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1 [8].

Chemical compound and disease context of SSX1

• In the three cases, a reverse transcription-polymerase chain reaction (RT-PCR) using ribonucleic acid extracted from formalin-fixed, paraffin-embedded tissues detected SYT-SSX1 fusion gene transcripts resulting from translocation t(X;18)(p11.2;q11.2), which is specific for synovial sarcoma [9].

Biological context of SSX1

• A novel fusion gene, SS18L1/SSX1, in synovial sarcoma [10].
• The breakpoint-associated genes were recently isolated: SYT, from chromosome 18, and SSX1 and SSX2, both from the X chromosome [11].
• 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 [12].
• In our repressor assay SSX1- and SSX2-KRAB domains down-modulated the transactivation of a reporter gene by threefold, compared with 83-fold repression achieved by KOX1-KRAB in the assay [13].
• The SYT-SSX1 fusion type of synovial sarcoma is associated with increased expression of cyclin A and D1. A link between t(X;18)(p11.2; q11.2) and the cell cycle machinery [14].

Anatomical context of SSX1

• We present evidence that SYT-SSX1 induces insulin-like growth factor II expression in fibroblast cells [8].
• SSX1, 2, 4 and 5 mRNA expression can be induced in cell lines by 5-aza-2-deoxycytidine or Trichostatin A [15].
• Four (SSX1, 2, 4 and 5) are known to be expressed in a subset of tumors and testis, and anti-SSX antibodies have been found in sera from cancer patients [15].
• Somatic cell hybrid analysis indicated that SSX3 maps within Xp11.2 --> p11.1, the region that also harbors the SSX1 and SSX2 genes [16].
• One lesion with histologic, immunohistologic, and ultrastructural features indeterminate for a diagnosis of synovial sarcoma or malignant peripheral nerve sheath tumor was studied and was positive for SYT-SSX1 [17].

Other interactions of SSX1

• Long-range organization of reiterated sequences, including the SSX1 cDNA at the OATL1 cluster in Xp11.23 [18].
• The aims of this study were to determine the expression and immunogenicity of these antigens in patients with epithelial ovarian cancer (EOC).EXPERIMENTAL DESIGN: SSX-1-, SSX-2-, and SSX-4-specific reverse transcription-PCR were done on a panel of EOC specimens [19].
• The SYT-SSX1 type fusion was associated with high Ki-67 expression (P = .011) and high mitotic rate (P = .070) [20].
• Both neoplasms contained the SYT-SSX1 type of the diagnostic translocation t(X;18) as detected by the reverse-transcription polymerase chain reaction analysis [21].

Analytical, diagnostic and therapeutic context of SSX1

• Dual colour fluorescence in situ hybridization to paraffin-embedded samples to deduce the presence of the der(X)t(X;18)(p11.2;q11.2) and involvement of either the SSX1 or SSX2 gene: a diagnostic and prognostic aid for synovial sarcoma [22].
• Subsequent sequence analysis revealed that one third of these clones represent an SSX gene that differs from both SSX1 and SSX2 [16].
• HER-2/neu expression by immunohistochemistry in synovial sarcomas was restricted to tumors with the SYT/SSX1 translocations [23].
• Molecular diagnosis of synovial sarcoma: RT-PCR detection of SYT-SSX1/2 fusion transcripts in paraffin-embedded tissue [24].
• A poorly differentiated synovial sarcoma (SYT/SSX1) expresses neuroectodermal markers: a xenografts and in vitro culture study [25].

References