Atlas of Genetics and Cytogenetics in Oncology and Haematology


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SSX2 (synovial sarcoma, X breakpoint 2)

Identity

Other namesCT5.2
HD21
HOM-MEL-40
MGC119055
MGC15364
MGC3884
SSX
SSX2A
SSX2B
HGNC (Hugo) SSX2
LocusID (NCBI) 6757
Location Xp11.22
Location_base_pair Starts at 52780280 and ends at 52790617 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Note SSX2 is a member of a family of at least nine genes (SSX1, SSX2, SSX3, SSX4, SSX5, SSX6, SSX7, SSX8 and SSX9) and ten pseudogenes (ψSSX1-10), all arranged in two clusters on the X chromosome, except ψSSX10 (Gure et al., 2002).
 
  SSX2 locus and mRNA splice variants. Note: Exons are drawn to scale.
Description The SSX2 gene locus encompasses 9 exons and 10304 bp (Xp11; 52725946-52736249).
Transcription The SSX2 gene is transcribed on the minus strand. 7 SSX2 mRNA splice variants (SV1-SV7) have been detected in liver, testis, skin melanoma, endometrium, choriocarcinoma, placenta, spleen of Hodgkins lymphoma.

Protein

Note SSX2 is gaining importance as a developmental factor involved in the pathogenesis of synovial sarcoma, and as an immunotherapeutic target for several human cancers.
 
  SSX2 protein isoforms. mRNAs and protein composition of SSX2 isoforms a and b. Open boxes are non-coding exons.
Description So far, two SSX2 protein isoforms (a and b) are known to exist. Their mRNAs correspond to SV1 (1466 bases) and SV3 (1322 bases) splice variants, respectively. The start codon for both isoforms is located in exon 2. SSX2 isoform a is 233 amino acids (26.5 kD) and SSX2 isoform b 188 amino acids (21.6 kD). Of both isoforms, SSX2 isoform b is the most commonly seen and so far the best studied.
Expression SSX2 is a nuclear protein normally expressed at high levels in the developing and normal adult testis (Apale and B spermatogonia) (Chen et al., 2011; Lim et al., 2011), and less abundantly in the thyroid gland (Crew et al., 1995). Its structural analysis (Lim et al., 1998) revealed two functional domains; an N-terminal region (amino acids 20-83) homologous to a Kruppel-associated box (KRAB) and a C-terminal 33 amino acids domain (amino acids 155-188) with a potent transcription repressor activity (SSXRD). KRAB boxes are usually present in zinc finger proteins and are implicated in transcription repression. SSX2 lacks DNA binding motifs and is thought to function in gene regulation through interaction with other transcription regulators. It contains a high density of charged amino acids (about 40%) and several consensus motifs for tyrosine phosphorylation and N-glycosylation.
Localisation SSX2 is usually localized in the nucleus (dos Santos et al., 2000). However, cytoplasmic SSX2 was detected in pluripotent mesenchymal stem cells before differentiation (Cronwright et al., 2005).
Function SSX2 is thought to function in germ line cell development (Chen et al., 2011) as a repressive gene regulator. Its control of gene expression is believed to be epigenetic in nature and to involve chromatin modification and remodeling. This is likely mediated by SSX2 association with the Polycomb gene-silencing complex at the SSXRD domain (Soulez et al., 1999; Barco et al., 2009; Przybyl et al., 2012), and with histones (Kato et al., 2002). Polycomb silencing involves chromatin compaction, DNA methylation, repressive histone modifications and inaccessibility of promoter regions to transcription machineries. Other SSX2-interacting partners include the LIM homeobox protein LHX4 (de Bruijn et al., 2008), a Ras-like GTPase Interactor, RAB3IP (de Bruijn et al., 2002) thought to be involved in vesicular transport, and SSX2IP, a putative cell cycle/circadian rhythm regulator. SSX2IP expression on the surface of myeloid leukemia cells (AML) marks it as an appropriate target for AML immunotherapy (Breslin et al., 2007). Recent evidence demonstrated a role for SSX2IP in promoting hepatocellular tumor metastasis and resistance to chemotherapy (Li et al., 2013).
Active studies are beginning to yield insights into SSX2 biological functions. Recent evidence demonstrated a regulatory role for SSX2 in nuclear receptor signaling and cancer cell invasion (Chen et al., 2012). A similar SSX2 effect on stem cell migration was reported previously (Cronwright et al., 2005).
Homology Human SSX2 is a member of a nine-gene family (SSX1, SSX2, SSX3, SSX4, SSX5, SSX6, SSX7, SSX8 and SSX9) located on the X chromosome. The SSX proteins are highly homologous at the nucleotide (about 90%) and the protein level (80%-90%). They are encoded by six exons and their expression is normally confined to testis (Gure et al., 1997; Gure et al., 2002). Recently, a mouse SSX gene family with 13 members and conserved KRAB and SSXRD domains has been identified (Chen et al., 2003).

Implicated in

Entity Synovial sarcoma
Note Synovial sarcoma (SS) is an aggressive soft tissue tumor that afflicts young adults between 15 and 40 years of age. Though its cell of origin is still unknown, it is thought to be a mesenchymal stem cell (Haldar et al., 2007; Naka et al., 2010). Synovial sarcomas most frequently arise in the para-articular areas, but are also known to appear in other tissues such as the lung, heart, kidney, stomach, intestine, the abdomen, head and neck, and the nervous system (Ferrari et al., 2008).
Synovial sarcoma is characterized by a unique chromosomal translocation event, t(X;18)(p11.2;q11.2) that involves a break in the SS18 gene on chromosome 18 and another in a SSX gene on the X chromosome. When fusion occurs at the breakpoints, it generates a hybrid gene, SS18-SSX, which encodes a potent oncogene. SS18-SSX is thought to initiate tumorigenesis and contribute to the development of synovial sarcoma (Ladanyi, 2001; Przybyl et al., 2012).
The t(X;18) tanslocation is the hallmark of synovial sarcomas. SS18-SSX is present in over 95% of SS cases. Its presence in human tumors is therefore of considerable diagnostic value and is usually detected using FISH, RT-PCR, qPCR or real time PCR (Amary et al., 2007; Ten Heuvel et al., 2008).
Of the nine members of the SSX family, the SSX1 and SSX2 gene loci are the most frequent sites of breakage in SS, and occasionally SSX4. The break in SSX occurs at the beginning of exon 6. According to cDNA sequence data, the SSX2 component contained in the SS18-SSX2 oncogene consists of exons 6 and 8. They represent the last 78 amino acids of SSX2 isoform b. This region lacks the KRAB repressive domain but retains the SSXRD region (Crew et al., 1995; de Leeuw et al., 1995; Wei et al., 2003).
SS presents in two distinct morphologies, monophasic, populated by spindle tumor cells, and biphasic with an additional glandular epithelial component. Several studies have demonstrated a strong correlation between the translocation subtype, tumor morphology and the clinical course of the disease. While the majority of SS18-SSX2 containing tumors were found to be monophasic, SS18-SSX1 was mostly detected in the biphasic tumors and was associated with a shorter metastasis-free period and a worse prognosis (Kawai et al., 1998; Antonescu et al., 2000; Ladanyi et al., 2002; Fernebro et al., 2006). However, the notion of the SS18-SSX subtype as a prognostic parameter influencing disease progression is still controversial due to contradictory data from later studies (Guillou et al., 2004; Ladanyi, 2005).
The molecular function of SS18-SSX is key to cancer development (dos Santos et al., 2001; de Bruijn et al., 2007; Przybyl et al., 2012). Fusion of SSX1/2 to SS18 results in the disruption of SS18 and its associated chromatin-remodeling/coactivator complexes (SWI/SNF, p300) normal function in gene expression (de Bruijn et al., 2006). SSX affinity for developmental genes controlled by Polycomb leads to the deregulation of such genes by SS18-SSX1/2 (Barco et al., 2009; Su et al., 2012). Deregulation of expression programs by SS18-SSX1/2 results in a series of biological events implicated in synovial sarcoma pathogenesis. These events likely include reprogramming of stem cell differentiation (Garcia et al., 2012), and untimely activation of oncogenic pathways such as IGF2 (Sun et al., 2006), Wnt (Horvai et al., 2006; Pretto et al., 2006; Bozzi et al., 2008), FGF (Ishibe et al., 2005; Garcia et al., 2012), and ephrin (Barco et al., 2007), as well as reactivation of the anti-apoptotic pathway and the bcl-2 oncogene (Mancuso et al., 2000, Jones et al., 2013).
SS18-SSX2 variants are rare. One was described by Fligman et al (1995). It contains an additional 126 bp segment proximal to SSX2 Exon 6, where the break occurred in Exon 5 while maintaining the frame. Another SS18-SSX2 variant includes 50 additional base pairs of SSX2 Exon 5 (Otsuka et al., 2006).
 
SS18-SSX fusion protein generated by the t(X;18)(p11.2;q11.2) chromosomal translocation. (X) represents cross-over. Arrowheads indicate breakpoints on SS18 and SSX.
Hybrid/Mutated Gene SS18-SSX2.
  
Entity Cancer / testis antigen reactivated in several cancers (CT antigen-SSX2, HOM-MEL40, CT5.2)
Note SSX2 is a major prototype of CT antigens (e.g. MAGE, GAGE, NY-Eso-1), a group of proteins whose expression is restricted to testis and human cancers. A large subset of CT antigen genes (over 30), including the SSX family, are located on the X chromosome, and are, for reasons unknown, aberrantly reactivated in several major cancers. The complete absence of CT antigen expression in normal tissues renders them ideal targets for cancer immunotherapy (Gure et al., 1997; Simpson et al., 2005; Smith and McNeel, 2010; Lim et al., 2012).
Disease Immunogenic response to reactivated SSX2 was first discovered in the sera of patients with malignant melanoma (Tureci et al., 1996). Since then aberrant expression of SSX2 has been detected in a large array of human cancers: skin melanoma (Tureci et al., 1998), breast cancer (Tureci et al., 1998; Mashino et al., 2001), endometrial cancer (Tureci et al., 1998), lung cancer (Gure et al., 2005), bladder cancer (Tureci et al., 1998), head-neck cancer (Tureci et al., 1998; Atanackovic et al., 2006), synovial sarcoma (Tureci et al., 1998), multiple myeloma (Taylor et al., 2005), colorectal carcinoma (Tureci et al., 1998; Scanlan et al., 2002), hepatocellular carcinoma (Chen et al., 2001; Bricard et al., 2005; Wu et al., 2006), prostate cancer (Dubovsky and McNeel, 2007; Smith and McNeel, 2011), glioma (Tureci et al., 1996, Tureci et al., 1998), stomach cancer (Mashino et al., 2001), thyroid cancer (Tureci et al., 1996), lymphoma (Tureci et al., 1998; Colleoni et al., 2002), leukemia (Niemeyer et al., 2003), neuroblastoma (Chi et al., 2002), osteosarcoma (Naka et al., 2002), ovarian cancer (Tureci et al., 1998; Valmori et al., 2006), and kidney cancer (Du et al., 2005).
Prognosis In several cancers, SSX2 and other CT antigens are considered diagnostic and prognostic markers of advanced malignancy. In multiple myeloma, non-small cell lung cancer, prostate cancer, and colorectal cancer, their coordinate expression is correlated with markedly reduced survival (Dubovsky and McNeel, 2007; Gure et al., 2005; Taylor et al., 2005) and metastasis (Choi and Chang, 2012).

Immunotherapy:
The high immunogenicity of CT antigens and their tissue-restricted expression make them optimal targets for tumor immunotherapy and vaccine development. SSX2 is a major tumor antigen. Due to SSX2 wide expression in cancer, a single anti-SSX2 therapy will potentially benefit multiple diseases. Immunodominant SSX2-derived peptides that elicit adequate T-cell responses have been identified, and initial reports have described their successful use in vivo (Wagner et al., 2003; Ayyoub et al., 2004a; Ayyoub et al., 2004b; Neumann et al., 2004; Ayyoub et al., 2005; Kyyamova et al., 2006; Huang et al., 2007; Neumann et al., 2011; Smith and McNeel, 2011). Since the majority of tumors express more than one CT antigen, attempts at generating polyvalent T cells directed against multiple epitopes for simultaneous antigen recognition are ongoing (Gerdemann et al., 2011; Smith et al., 2011). Notably, CT antigen-specific cytotoxic T lymphocytes were able to recognize and destroy chemoresistant lymphoma cells expressing the cognate antigens (Shafer et al., 2010). Finally, CT antigen directed immunotherapy could potentially become a valuable addition to chemotherapy for effective treatment of cancer.

  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945 MedulloblastomaID5065

External links

Nomenclature
HGNC (Hugo)SSX2   11336
Cards
AtlasSSX2ID42406chXp11
Entrez_Gene (NCBI)SSX2  6757  synovial sarcoma, X breakpoint 2
GeneCards (Weizmann)SSX2
Ensembl (Hinxton)ENSG00000241476 [Gene_View]  chrX:52780280-52790617 [Contig_View]  SSX2 [Vega]
ICGC DataPortalENSG00000241476
cBioPortalSSX2
AceView (NCBI)SSX2
Genatlas (Paris)SSX2
WikiGenes6757
SOURCE (Princeton)NM_001278697 NM_003147 NM_175698
Genomic and cartography
GoldenPath (UCSC)SSX2  -  Xp11.22   chrX:52780280-52790617 +  Xp11.22   [Description]    (hg19-Feb_2009)
EnsemblSSX2 - Xp11.22 [CytoView]
Mapping of homologs : NCBISSX2 [Mapview]
OMIM300192   300813   
Gene and transcription
Genbank (Entrez)AF190791 AM393802 BC002818 BC007343 BC016957
RefSeq transcript (Entrez)NM_001278697 NM_003147 NM_175698
RefSeq genomic (Entrez)AC_000155 NC_000023 NC_018934 NT_011630 NW_001842368 NW_004929442
Consensus coding sequences : CCDS (NCBI)SSX2
Cluster EST : UnigeneHs.661107 [ NCBI ]
CGAP (NCI)Hs.661107
Alternative Splicing : Fast-db (Paris)GSHG0032955
Alternative Splicing GalleryENSG00000241476
Gene ExpressionSSX2 [ NCBI-GEO ]     SSX2 [ SEEK ]   SSX2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ16385 (Uniprot)
NextProtQ16385  [Medical]
With graphics : InterProQ16385
Splice isoforms : SwissVarQ16385 (Swissvar)
Domaine pattern : Prosite (Expaxy)KRAB_RELATED (PS50806)   
Domains : Interpro (EBI)Krueppel-associated_box [organisation]   Krueppel-associated_box-rel [organisation]   SSX [organisation]   SSXRD_motif [organisation]  
Related proteins : CluSTrQ16385
Domain families : Pfam (Sanger)KRAB (PF01352)    SSXRD (PF09514)   
Domain families : Pfam (NCBI)pfam01352    pfam09514   
Domain families : Smart (EMBL)KRAB (SM00349)  
DMDM Disease mutations6757
Blocks (Seattle)Q16385
Human Protein AtlasENSG00000241476 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ16385
HPRD02180
IPIIPI00001520   IPI00305877   IPI00879105   
Protein Interaction databases
DIP (DOE-UCLA)Q16385
IntAct (EBI)Q16385
FunCoupENSG00000241476
BioGRIDSSX2
InParanoidQ16385
Interologous Interaction database Q16385
IntegromeDBSSX2
STRING (EMBL)SSX2
Ontologies - Pathways
Ontology : AmiGO
Ontology : EGO-EBI
Pathways : KEGGTranscriptional misregulation in cancer   
Protein Interaction DatabaseSSX2
Wikipedia pathwaysSSX2
Gene fusion - rearrangments
Rearrangement : COSMICSS18 [18q11.2]  -  SSX2 [Xp11.22]  
  [COSF500] [COSF501] [COSF516] [COSF517] [COSF523] [COSF530] [COSF567] [COSF573] [COSF574] 
  [COSF579] [COSF583] [COSF584] [COSF587] 
Rearrangement : COSMICSSX2 [Xp11.22]  -  SS18 [18q11.2]  
  [COSF524] [COSF576] [COSF580] [COSF585] [COSF586] 
Rearrangement : TICdbSS18 [18q11.2]  -  SSX2 [1q23.1]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)SSX2
snp3D : Map Gene to Disease6757
SNP (GeneSNP Utah)SSX2
SNP : HGBaseSSX2
Genetic variants : HAPMAPSSX2
Exome VariantSSX2
1000_GenomesSSX2 
ICGC programENSG00000241476 
Cancer Gene: CensusSSX2 
Somatic Mutations in Cancer : COSMICSSX2 
CONAN: Copy Number AnalysisSSX2 
Mutations and Diseases : HGMDSSX2
Mutations and Diseases : intOGenSSX2
Genomic VariantsSSX2  SSX2 [DGVbeta]
dbVarSSX2
ClinVarSSX2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM300192    300813   
MedgenSSX2
GENETestsSSX2
Disease Genetic AssociationSSX2
Huge Navigator SSX2 [HugePedia]  SSX2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneSSX2
Homology/Alignments : Family Browser (UCSC)SSX2
Phylogenetic Trees/Animal Genes : TreeFamSSX2
Chemical/Protein Interactions : CTD6757
Chemical/Pharm GKB GenePA36160
Clinical trialSSX2
Cancer Resource (Charite)ENSG00000241476
Other databases
Probes
Litterature
PubMed40 Pubmed reference(s) in Entrez
CoreMineSSX2
iHOPSSX2
OncoSearchSSX2

Bibliography

Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma.
Crew AJ, Clark J, Fisher C, Gill S, Grimer R, Chand A, Shipley J, Gusterson BA, Cooper CS.
EMBO J. 1995 May 15;14(10):2333-40.
PMID 7539744
 
Identification of two alternative fusion genes, SYT-SSX1 and SYT-SSX2, in t(X;18)(p11.2;q11.2)-positive synovial sarcomas.
de Leeuw B, Balemans M, Olde Weghuis D, Geurts van Kessel A.
Hum Mol Genet. 1995 Jun;4(6):1097-9.
PMID 7655467
 
Molecular diagnosis of synovial sarcoma and characterization of a variant SYT-SSX2 fusion transcript.
Fligman I, Lonardo F, Jhanwar SC, Gerald WL, Woodruff J, Ladanyi M.
Am J Pathol. 1995 Dec;147(6):1592-9.
PMID 7495284
 
The SSX-2 gene, which is involved in the t(X;18) translocation of synovial sarcomas, codes for the human tumor antigen HOM-MEL-40.
Tureci O, Sahin U, Schobert I, Koslowski M, Scmitt H, Schild HJ, Stenner F, Seitz G, Rammensee HG, Pfreundschuh M.
Cancer Res. 1996 Oct 15;56(20):4766-72.
PMID 8840996
 
SSX: a multigene family with several members transcribed in normal testis and human cancer.
Gure AO, Tureci O, Sahin U, Tsang S, Scanlan MJ, Jager E, Knuth A, Pfreundschuh M, Old LJ, Chen YT.
Int J Cancer. 1997 Sep 17;72(6):965-71.
PMID 9378559
 
SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma.
Kawai A, Woodruff J, Healey JH, Brennan MF, Antonescu CR, Ladanyi M.
N Engl J Med. 1998 Jan 15;338(3):153-60.
PMID 9428816
 
A KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas.
Lim FL, Soulez M, Koczan D, Thiesen HJ, Knight JC.
Oncogene. 1998 Oct 15;17(15):2013-8.
PMID 9788446
 
Expression of SSX genes in human tumors.
Tureci O, Chen YT, Sahin U, Gure AO, Zwick C, Villena C, Tsang S, Seitz G, Old LJ, Pfreundschuh M.
Int J Cancer. 1998 Jul 3;77(1):19-23.
PMID 9639388
 
SSX and the synovial-sarcoma-specific chimaeric protein SYT-SSX co-localize with the human Polycomb group complex.
Soulez M, Saurin AJ, Freemont PS, Knight JC.
Oncogene. 1999 Apr 29;18(17):2739-46.
PMID 10348348
 
Strong association of SYT-SSX fusion type and morphologic epithelial differentiation in synovial sarcoma.
Antonescu CR, Kawai A, Leung DH, Lonardo F, Woodruff JM, Healey JH, Ladanyi M.
Diagn Mol Pathol. 2000 Mar;9(1):1-8.
PMID 10718206
 
Delineation of the protein domains responsible for SYT, SSX, and SYT-SSX nuclear localization.
dos Santos NR, de Bruijn DR, Kater-Baats E, Otte AP, van Kessel AG.
Exp Cell Res. 2000 Apr 10;256(1):192-202.
PMID 10739666
 
Analysis of SYT-SSX fusion transcripts and bcl-2 expression and phosphorylation status in synovial sarcoma.
Mancuso T, Mezzelani A, Riva C, Fabbri A, Dal Bo L, Sampietro G, Perego P, Casali P, Zunino F, Sozzi G, Pierotti MA, Pilotti S.
Lab Invest. 2000 Jun;80(6):805-13.
PMID 10879732
 
Expressions of cancer-testis antigens in human hepatocellular carcinomas.
Chen CH, Chen GJ, Lee HS, Huang GT, Yang PM, Tsai LJ, Chen DS, Sheu JC.
Cancer Lett. 2001 Mar 26;164(2):189-95.
PMID 11179834
 
Molecular mechanisms underlying human synovial sarcoma development.
dos Santos NR, de Bruijn DR, van Kessel AG.
Genes Chromosomes Cancer. 2001 Jan;30(1):1-14. (REVIEW)
PMID 11107170
 
Fusions of the SYT and SSX genes in synovial sarcoma.
Ladanyi M.
Oncogene. 2001 Sep 10;20(40):5755-62. (REVIEW)
PMID 11607825
 
Expression of multiple cancer-testis antigen genes in gastrointestinal and breast carcinomas.
Mashino K, Sadanaga N, Tanaka F, Yamaguchi H, Nagashima H, Inoue H, Sugimachi K, Mori M.
Br J Cancer. 2001 Sep 1;85(5):713-20.
PMID 11531257
 
Expression of SSX-2 and SSX-4 genes in neuroblastoma.
Chi SN, Cheung NK, Cheung IY.
Int J Biol Markers. 2002 Oct-Dec;17(4):219-23.
PMID 12521124
 
Expression of SSX genes in the neoplastic cells of Hodgkin's lymphoma.
Colleoni GW, Capodieci P, Tickoo S, Cossman J, Filippa DA, Ladanyi M.
Hum Pathol. 2002 May;33(5):496-502.
PMID 12094374
 
The cancer-related protein SSX2 interacts with the human homologue of a Ras-like GTPase interactor, RAB3IP, and a novel nuclear protein, SSX2IP.
de Bruijn DR, dos Santos NR, Kater-Baats E, Thijssen J, van den Berk L, Stap J, Balemans M, Schepens M, Merkx G, van Kessel AG.
Genes Chromosomes Cancer. 2002 Jul;34(3):285-98.
PMID 12007189
 
The SSX gene family: characterization of 9 complete genes.
Gure AO, Wei IJ, Old LJ, Chen YT.
Int J Cancer. 2002 Oct 10;101(5):448-53.
PMID 12216073
 
SYT associates with human SNF/SWI complexes and the C-terminal region of its fusion partner SSX1 targets histones.
Kato H, Tjernberg A, Zhang W, Krutchinsky AN, An W, Takeuchi T, Ohtsuki Y, Sugano S, de Bruijn DR, Chait BT, Roeder RG.
J Biol Chem. 2002 Feb 15;277(7):5498-505. Epub 2001 Dec 4.
PMID 11734557
 
Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients.
Ladanyi M, Antonescu CR, Leung DH, Woodruff JM, Kawai A, Healey JH, Brennan MF, Bridge JA, Neff JR, Barr FG, Goldsmith JD, Brooks JS, Goldblum JR, Ali SZ, Shipley J, Cooper CS, Fisher C, Skytting B, Larsson O.
Cancer Res. 2002 Jan 1;62(1):135-40.
PMID 11782370
 
Expression of SSX genes in human osteosarcomas.
Naka N, Araki N, Nakanishi H, Itoh K, Mano M, Ishiguro S, de Bruijn DR, Myoui A, Ueda T, Yoshikawa H.
Int J Cancer. 2002 Apr 1;98(4):640-2.
PMID 11920629
 
Cancer-related serological recognition of human colon cancer: identification of potential diagnostic and immunotherapeutic targets.
Scanlan MJ, Welt S, Gordon CM, Chen YT, Gure AO, Stockert E, Jungbluth AA, Ritter G, Jager D, Jager E, Knuth A, Old LJ.
Cancer Res. 2002 Jul 15;62(14):4041-7.
PMID 12124339
 
Identification and characterization of mouse SSX genes: a multigene family on the X chromosome with restricted cancer/testis expression.
Chen YT, Alpen B, Ono T, Gure AO, Scanlan MA, Biggs WH 3rd, Arden K, Nakayama E, Old LJ.
Genomics. 2003 Dec;82(6):628-36.
PMID 14611804
 
Expression of serologically identified tumor antigens in acute leukemias.
Niemeyer P, Tureci O, Eberle T, Graf N, Pfreundschuh M, Sahin U.
Leuk Res. 2003 Jul;27(7):655-60.
PMID 12681366
 
Identification of an HLA-A*02 restricted immunogenic peptide derived from the cancer testis antigen HOM-MEL-40/SSX2.
Wagner C, Neumann F, Kubuschok B, Regitz E, Mischo A, Stevanovic S, Friedrich M, Schmidt W, Rammensee HG, Pfreundschuh M.
Cancer Immun. 2003 Dec 17;3:18.
PMID 14677925
 
Characteristic sequence motifs located at the genomic breakpoints of the translocation t(X;18) in synovial sarcomas.
Wei Y, Sun M, Nilsson G, Dwight T, Xie Y, Wang J, Hou Y, Larsson O, Larsson C, Zhu X.
Oncogene. 2003 Apr 10;22(14):2215-22.
PMID 12687023
 
Identification of an SSX-2 epitope presented by dendritic cells to circulating autologous CD4+ T cells.
Ayyoub M, Hesdorffer CS, Metthez G, Stevanovic S, Ritter G, Chen YT, Old LJ, Speiser D, Cerottini JC, Valmori D.
J Immunol. 2004a Jun 1;172(11):7206-11.
PMID 15153546
 
An immunodominant SSX-2-derived epitope recognized by CD4+ T cells in association with HLA-DR.
Ayyoub M, Hesdorffer CS, Montes M, Merlo A, Speiser D, Rimoldi D, Cerottini JC, Ritter G, Scanlan M, Old LJ, Valmori D.
J Clin Invest. 2004b Apr;113(8):1225-33.
PMID 15085202
 
Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: a multicenter, retrospective analysis.
Guillou L, Benhattar J, Bonichon F, Gallagher G, Terrier P, Stauffer E, Somerhausen Nde S, Michels JJ, Jundt G, Vince DR, Taylor S, Genevay M, Collin F, Trassard M, Coindre JM.
J Clin Oncol. 2004 Oct 15;22(20):4040-50. Epub 2004 Sep 13.
PMID 15364967
 
Identification of an HLA-DR-restricted peptide epitope with a promiscuous binding pattern derived from the cancer testis antigen HOM-MEL-40/SSX2.
Neumann F, Wagner C, Stevanovic S, Kubuschok B, Schormann C, Mischo A, Ertan K, Schmidt W, Pfreundschuh M.
Int J Cancer. 2004 Nov 20;112(4):661-8.
PMID 15382048
 
Distinct but overlapping T helper epitopes in the 37-58 region of SSX-2.
Ayyoub M, Merlo A, Hesdorffer CS, Speiser D, Rimoldi D, Cerottini JC, Ritter G, Chen YT, Old LJ, Stevanovic S, Valmori D.
Clin Immunol. 2005 Jan;114(1):70-8.
PMID 15596411
 
Naturally acquired MAGE-A10- and SSX-2-specific CD8+ T cell responses in patients with hepatocellular carcinoma.
Bricard G, Bouzourene H, Martinet O, Rimoldi D, Halkic N, Gillet M, Chaubert P, Macdonald HR, Romero P, Cerottini JC, Speiser DE.
J Immunol. 2005 Feb 1;174(3):1709-16.
PMID 15661935
 
Cancer/testis antigen expression in human mesenchymal stem cells: down-regulation of SSX impairs cell migration and matrix metalloproteinase 2 expression.
Cronwright G, Le Blanc K, Gotherstrom C, Darcy P, Ehnman M, Brodin B.
Cancer Res. 2005 Mar 15;65(6):2207-15.
PMID 15781633
 
Expression of SSX2 gene in human urologic neoplasms.
Du P, Yu LZ, Ma M, Geng L, Wang XS, Xin DQ, Na YQ.
Zhonghua Wai Ke Za Zhi. 2005 Mar 15;43(6):379-81.
PMID 15854347
 
Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer.
Gure AO, Chua R, Williamson B, Gonen M, Ferrera CA, Gnjatic S, Ritter G, Simpson AJ, Chen YT, Old LJ, Altorki NK.
Clin Cancer Res. 2005 Nov 15;11(22):8055-62.
PMID 16299236
 
Disruption of fibroblast growth factor signal pathway inhibits the growth of synovial sarcomas: potential application of signal inhibitors to molecular target therapy.
Ishibe T, Nakayama T, Okamoto T, Aoyama T, Nishijo K, Shibata KR, Shima Y, Nagayama S, Katagiri T, Nakamura Y, Nakamura T, Toguchida J.
Clin Cancer Res. 2005 Apr 1;11(7):2702-12.
PMID 15814652
 
Correlates of SYT-SSX fusion type in synovial sarcoma: getting more complex but also more interesting?
Ladanyi M.
J Clin Oncol. 2005 May 20;23(15):3638-9; author reply 3639-40.
PMID 15908683
 
Cancer/testis antigens, gametogenesis and cancer.
Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ.
Nat Rev Cancer. 2005 Aug;5(8):615-25.
PMID 16034368
 
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.
Taylor BJ, Reiman T, Pittman JA, Keats JJ, de Bruijn DR, Mant MJ, Belch AR, Pilarski LM.
J Immunother. 2005 Nov-Dec;28(6):564-75.
PMID 16224274
 
Expression of cancer-testis antigens as possible targets for antigen-specific immunotherapy in head and neck squamous cell carcinoma.
Atanackovic D, Blum I, Cao Y, Wenzel S, Bartels K, Faltz C, Hossfeld DK, Hegewisch-Becker S, Bokemeyer C, Leuwer R.
Cancer Biol Ther. 2006 Sep;5(9):1218-25. Epub 2006 Sep 9.
PMID 16929165
 
The synovial-sarcoma-associated SS18-SSX2 fusion protein induces epigenetic gene (de)regulation.
de Bruijn DR, Allander SV, van Dijk AH, Willemse MP, Thijssen J, van Groningen JJ, Meltzer PS, van Kessel AG.
Cancer Res. 2006 Oct 1;66(19):9474-82.
PMID 17018603
 
Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma.
Fernebro J, Francis P, Eden P, Borg A, Panagopoulos I, Mertens F, Vallon-Christersson J, Akerman M, Rydholm A, Bauer HC, Mandahl N, Nilbert M.
Int J Cancer. 2006 Mar 1;118(5):1165-72.
PMID 16152617
 
Beta-catenin nuclear expression correlates with cyclin D1 expression in primary and metastatic synovial sarcoma: a tissue microarray study.
Horvai AE, Kramer MJ, O'Donnell R.
Arch Pathol Lab Med. 2006 Jun;130(6):792-8.
PMID 16740029
 
Expression of SSX2 tumor antigen in baculovirus expression system and its application for screening of blood serum of melanoma patients.
Kyyamova RG, Gryshkova VS, Zhyvoloup AM.
Exp Oncol. 2006 Jun;28(2):110-3.
PMID 16837900
 
A variant of the SYT-SSX2 fusion gene in a case of synovial sarcoma.
Otsuka S, Nishijo K, Nakayama T, Aoyama T, Ishibe T, Shibata KR, Shima Y, Nakamura T, Otsuka T, Toguchida J.
Cancer Genet Cytogenet. 2006 May;167(1):82-8.
PMID 16682293
 
The synovial sarcoma translocation protein SYT-SSX2 recruits beta-catenin to the nucleus and associates with it in an active complex.
Pretto D, Barco R, Rivera J, Neel N, Gustavson MD, Eid JE.
Oncogene. 2006 Jun 22;25(26):3661-9. Epub 2006 Feb 6.
PMID 16462762
 
IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1.
Sun Y, Gao D, Liu Y, Huang J, Lessnick S, Tanaka S.
Oncogene. 2006 Feb 16;25(7):1042-52.
PMID 16247461
 
Expression of synovial sarcoma X (SSX) antigens in epithelial ovarian cancer and identification of SSX-4 epitopes recognized by CD4+ T cells.
Valmori D, Qian F, Ayyoub M, Renner C, Merlo A, Gnjatic S, Stockert E, Driscoll D, Lele S, Old LJ, Odunsi K.
Clin Cancer Res. 2006 Jan 15;12(2):398-404.
PMID 16428478
 
Expression of cancer-testis antigen (CTA) in tumor tissues and peripheral blood of Chinese patients with hepatocellular carcinoma.
Wu LQ, Lu Y, Wang XF, Lv ZH, Zhang B, Yang JY.
Life Sci. 2006 Jul 17;79(8):744-8. Epub 2006 Feb 28.
PMID 16546222
 
Detection of SS18-SSX fusion transcripts in formalin-fixed paraffin-embedded neoplasms: analysis of conventional RT-PCR, qRT-PCR and dual color FISH as diagnostic tools for synovial sarcoma.
Amary MF, Berisha F, Bernardi Fdel C, Herbert A, James M, Reis-Filho JS, Fisher C, Nicholson AG, Tirabosco R, Diss TC, Flanagan AM.
Mod Pathol. 2007 Apr;20(4):482-96. Epub 2007 Mar 2.
PMID 17334349
 
The synovial sarcoma SYT-SSX2 oncogene remodels the cytoskeleton through activation of the ephrin pathway.
Barco R, Hunt LB, Frump AL, Garcia CB, Benesh A, Caldwell RL, Eid JE.
Mol Biol Cell. 2007 Oct;18(10):4003-12. Epub 2007 Aug 8.
PMID 17686994
 
SSX2IP: an emerging role in cancer.
Breslin A, Denniss FA, Guinn BA.
Biochem Biophys Res Commun. 2007 Nov 23;363(3):462-5. Epub 2007 Sep 24. (REVIEW)
PMID 17904521
 
The (epi)genetics of human synovial sarcoma.
de Bruijn DR, Nap JP, van Kessel AG.
Genes Chromosomes Cancer. 2007 Feb;46(2):107-17. (REVIEW)
PMID 17117414
 
Inducible expression of a prostate cancer-testis antigen, SSX-2, following treatment with a DNA methylation inhibitor.
Dubovsky JA, McNeel DG.
Prostate. 2007 Dec 1;67(16):1781-90.
PMID 17929270
 
A conditional mouse model of synovial sarcoma: insights into a myogenic origin.
Haldar M, Hancock JD, Coffin CM, Lessnick SL, Capecchi MR.
Cancer Cell. 2007 Apr;11(4):375-88.
PMID 17418413
 
Expression and purification of the cancer antigen SSX2: a potential cancer vaccine.
Huang CJ, Chen RH, Vannelli T, Lee F, Ritter E, Ritter G, Old LJ, Batt CA.
Protein Expr Purif. 2007 Dec;56(2):212-9. Epub 2007 Aug 24.
PMID 17931884
 
Molecular characterization of synovial sarcoma in children and adolescents: evidence of akt activation.
Bozzi F, Ferrari A, Negri T, Conca E, Luca da R, Losa M, Casieri P, Orsenigo M, Lampis A, Meazza C, Casanova M, Pierotti MA, Tamborini E, Pilotti S.
Transl Oncol. 2008 Jul;1(2):95-101.
PMID 18633459
 
The C terminus of the synovial sarcoma-associated SSX proteins interacts with the LIM homeobox protein LHX4.
de Bruijn DR, van Dijk AH, Willemse MP, van Kessel AG.
Oncogene. 2008 Jan 24;27(5):653-62. Epub 2007 Jul 30.
PMID 17667940
 
Synovial sarcoma of children and adolescents: the prognostic role of axial sites.
Ferrari A, Bisogno G, Alaggio R, Cecchetto G, Collini P, Rosolen A, Meazza C, Indolfi P, Garaventa A, De Sio L, D'Angelo P, Tamaro P, Casanova M, Carli M.
Eur J Cancer. 2008 Jun;44(9):1202-9. doi: 10.1016/j.ejca.2008.03.016. Epub 2008 Apr 25.
PMID 18440800
 
Diagnostic accuracy of FISH and RT-PCR in 50 routinely processed synovial sarcomas.
Ten Heuvel SE, Hoekstra HJ, Suurmeijer AJ.
Appl Immunohistochem Mol Morphol. 2008 May;16(3):246-50. doi: 10.1097/PAI.0b013e31815349f5.
PMID 18301245
 
The synovial sarcoma-associated SYT-SSX2 oncogene antagonizes the polycomb complex protein Bmi1.
Barco R, Garcia CB, Eid JE.
PLoS One. 2009;4(4):e5060. doi: 10.1371/journal.pone.0005060. Epub 2009 Apr 1.
PMID 19337376
 
Synovial sarcoma is a stem cell malignancy.
Naka N, Takenaka S, Araki N, Miwa T, Hashimoto N, Yoshioka K, Joyama S, Hamada K, Tsukamoto Y, Tomita Y, Ueda T, Yoshikawa H, Itoh K.
Stem Cells. 2010 Jul;28(7):1119-31. doi: 10.1002/stem.452.
PMID 20518020
 
Antigen-specific cytotoxic T lymphocytes can target chemoresistant side-population tumor cells in Hodgkin lymphoma.
Shafer JA, Cruz CR, Leen AM, Ku S, Lu A, Rousseau A, Heslop HE, Rooney CM, Bollard CM, Foster AE.
Leuk Lymphoma. 2010 May;51(5):870-80. doi: 10.3109/10428191003713968.
PMID 20367572
 
The SSX family of cancer-testis antigens as target proteins for tumor therapy.
Smith HA, McNeel DG.
Clin Dev Immunol. 2010;2010:150591. doi: 10.1155/2010/150591. Epub 2010 Oct 11. (REVIEW)
PMID 20981248
 
Chromosome X-encoded cancer/testis antigens show distinctive expression patterns in developing gonads and in testicular seminoma.
Chen YT, Chiu R, Lee P, Beneck D, Jin B, Old LJ.
Hum Reprod. 2011 Dec;26(12):3232-43. doi: 10.1093/humrep/der330. Epub 2011 Oct 20.
PMID 22016418
 
Cytotoxic T lymphocytes simultaneously targeting multiple tumor-associated antigens to treat EBV negative lymphoma.
Gerdemann U, Katari U, Christin AS, Cruz CR, Tripic T, Rousseau A, Gottschalk SM, Savoldo B, Vera JF, Heslop HE, Brenner MK, Bollard CM, Rooney CM, Leen AM.
Mol Ther. 2011 Dec;19(12):2258-68. doi: 10.1038/mt.2011.167. Epub 2011 Sep 13.
PMID 21915103
 
OCT2, SSX and SAGE1 reveal the phenotypic heterogeneity of spermatocytic seminoma reflecting distinct subpopulations of spermatogonia.
Lim J, Goriely A, Turner GD, Ewen KA, Jacobsen GK, Graem N, Wilkie AO, Rajpert-De Meyts E.
J Pathol. 2011 Aug;224(4):473-83. doi: 10.1002/path.2919. Epub 2011 Jun 27.
PMID 21706474
 
A peptide epitope derived from the cancer testis antigen HOM-MEL-40/SSX2 capable of inducing CD4+ and CD8+ T-cell as well as B-cell responses.
Neumann F, Kubuschok B, Ertan K, Schormann C, Stevanovic S, Preuss KD, Schmidt W, Pfreundschuh M.
Cancer Immunol Immunother. 2011 Sep;60(9):1333-46. doi: 10.1007/s00262-011-1030-6. Epub 2011 Jun 1.
PMID 21630107
 
Expression and immunotherapeutic targeting of the SSX family of cancer-testis antigens in prostate cancer.
Smith HA, Cronk RJ, Lang JM, McNeel DG.
Cancer Res. 2011 Nov 1;71(21):6785-95. doi: 10.1158/0008-5472.CAN-11-2127. Epub 2011 Aug 31.
PMID 21880588
 
Vaccines targeting the cancer-testis antigen SSX-2 elicit HLA-A2 epitope-specific cytolytic T cells.
Smith HA, McNeel DG.
J Immunother. 2011 Oct;34(8):569-80. doi: 10.1097/CJI.0b013e31822b5b1d.
PMID 21904219
 
Cancer/testis antigen SSX2 enhances invasiveness in MCF-7 cells by repressing ERalpha signaling.
Chen L, Zhou WB, Zhao Y, Liu XA, Ding Q, Zha XM, Wang S.
Int J Oncol. 2012 Jun;40(6):1986-94. doi: 10.3892/ijo.2012.1369. Epub 2012 Feb 13.
PMID 22344619
 
The expression of MAGE and SSX, and correlation of COX2, VEGF, and survivin in colorectal cancer.
Choi J, Chang H.
Anticancer Res. 2012 Feb;32(2):559-64.
PMID 22287745
 
Reprogramming of mesenchymal stem cells by the synovial sarcoma-associated oncogene SYT-SSX2.
Garcia CB, Shaffer CM, Alfaro MP, Smith AL, Sun J, Zhao Z, Young PP, VanSaun MN, Eid JE.
Oncogene. 2012 May 3;31(18):2323-34. doi: 10.1038/onc.2011.418. Epub 2011 Sep 26.
PMID 21996728
 
Deconstruction of the SS18-SSX fusion oncoprotein complex: insights into disease etiology and therapeutics.
Su L, Sampaio AV, Jones KB, Pacheco M, Goytain A, Lin S, Poulin N, Yi L, Rossi FM, Kast J, Capecchi MR, Underhill TM, Nielsen TO.
Cancer Cell. 2012 Mar 20;21(3):333-47. doi: 10.1016/j.ccr.2012.01.010.
PMID 22439931
 
SS18-SSX2 and the mitochondrial apoptosis pathway in mouse and human synovial sarcomas.
Jones KB, Su L, Jin H, Lenz C, Randall RL, Underhill TM, Nielsen TO, Sharma S, Capecchi MR.
Oncogene. 2013 May 2;32(18):2365-71, 2375.e1-5. doi: 10.1038/onc.2012.247. Epub 2012 Jul 16.
PMID 22797074
 
Cancer-testis antigens: the current status on antigen regulation and potential clinical use.
Lim SH, Zhang Y, Zhang J.
Am J Blood Res. 2012;2(1):29-35. Epub 2012 Jan 1.
PMID 22432085
 
Downstream and intermediate interactions of synovial sarcoma-associated fusion oncoproteins and their implication for targeted therapy.
Przybyl J, Jurkowska M, Rutkowski P, Debiec-Rychter M, Siedlecki JA.
Sarcoma. 2012;2012:249219. doi: 10.1155/2012/249219. Epub 2012 Mar 25.
PMID 22550415
 
Deconstruction of the SS18-SSX fusion oncoprotein complex: insights into disease etiology and therapeutics.
Su L, Sampaio AV, Jones KB, Pacheco M, Goytain A, Lin S, Poulin N, Yi L, Rossi FM, Kast J, Capecchi MR, Underhill TM, Nielsen TO.
Cancer Cell. 2012 Mar 20;21(3):333-47. doi: 10.1016/j.ccr.2012.01.010.
PMID 22439931
 
SSX2IP promotes metastasis and chemotherapeutic resistance of hepatocellular carcinoma.
Li P, Lin Y, Zhang Y, Zhu Z, Huo K.
J Transl Med. 2013 Mar 1;11:52. doi: 10.1186/1479-5876-11-52.
PMID 23452395
 
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Written04-2008Josiane Eid, Christina Garcia, Andrea Frump
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Updated05-2013Josiane Eid, Christina Garcia, Andrea Frump
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA

Citation

This paper should be referenced as such :
Eid, J ; Garcia, C ; Frump, A
SSX2 (synovial sarcoma, X breakpoint 2)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(11):759-765.
Free online version   Free pdf version   [Bibliographic record ]
History of this paper:
Eid, J ; Garcia, C ; Frump, A. SSX2 (synovial sarcoma, X breakpoint 2). Atlas Genet Cytogenet Oncol Haematol. 2013;17(11):759-765.
URL : http://AtlasGeneticsOncology.org/Genes/SSX2ID42406chXp11.html

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