Disease relevance of SSX2

• Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma [1].
• Three of the 13 antigens were cancer/testis antigens (MAGEA3, SSX2, and NY-ESO-1), which are expressed exclusively in normal gametogenic tissues and aberrantly expressed in a broad range of cancer types [2].
• 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 [3].
• Thirty-four of 101 primary and metastatic melanoma cases and 2 of 24 common nevocellular and atypical nevus cases showed SSX nuclear staining [4].
• Fifteen other sarcomas and related tumors were negative for SYT-SSX fusion transcripts [5].

High impact information on SSX2

• SYT sequences constitute the N-terminal segment of a fusion oncogene product, SYT-SSX, routinely detected in synovial sarcoma, an aggressive human tumor [6].
• The translocation fuses the SYT gene from chromosome 18 to either of two highly homologous genes at Xp11, SSX1 or SSX2 [7].
• SYT-SSX fusion transcripts are a defining diagnostic marker of synovial sarcomas and may also yield important independent prognostic information [7].
• SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma [7].
• There were no significant correlations between the type of SYT-SSX transcript and age, sex, tumor location and size, whether there were metastases at diagnosis, or whether patients underwent chemotherapy [7].

Chemical compound and disease context of SSX2

• Detection of the SYT-SSX fusion transcripts in formaldehyde-fixed, paraffin-embedded tissue: a reverse transcription polymerase chain reaction amplification assay useful in the diagnosis of synovial sarcoma [5].
• In this study, we conducted a reverse transcription-polymerase chain reaction-based assay to detect the SYT-SSX fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens from a series of 32 synovial sarcoma cases including 6 tumors found in unusual anatomical sites [8].
• To investigate the distribution of tumour cells expressing the SYT-SSX fusion gene in biphasic synovial sarcoma, modified reverse transcription polymerase chain reaction (RT-PCR) analysis was performed using microdissected specimens from haematoxylin and eosin stained sections of archival paraffin wax embedded tissues [9].

Biological context of SSX2

• As a result of this translocation the SYT gene on chromosome 18 fuses to either the SSX1 or the SSX2 gene on the X chromosome [10].
• Patients whose tumors contained the SYT-SSX2 fusion (P = 0.08) or were smaller (P = 0.12) showed a trend toward better survival by log-rank test, whereas tumor histology had no impact (P = 0.8) [11].
• 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 [3].
• Treatment of an SSX-negative cell line with 5-aza-2'-deoxycytidine, a demethylating agent, led to SSX RNA and protein expression, indicating a role for methylation in transcription regulation [4].
• We now report the analysis of the expression of all 5 SSX genes in 325 specimens of human neoplasms from various histological origins, using reverse transcription polymerase chain reaction (RT-PCR) [12].

Anatomical context of SSX2

• 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 [3].
• However, the number of reported cases was not sufficient to conclude that SYT-SSX2 fusion in biphasic synovial sarcoma of the thorax is, indeed, rare [13].
• Case 2 exhibited a biphasic synovial sarcoma of the mediastinum containing an SYT-SSX2 fusion transcript, which is a rare fusion type in biphasic synovial sarcomas of the limbs [13].
• Somatic cell hybrid analysis indicated that SSX3 maps within Xp11.2 --> p11.1, the region that also harbors the SSX1 and SSX2 genes [14].
• Of 18 melanoma cell lines analyzed, 9 showed SSX RNA and protein expression, although heterogeneously and at variable levels [4].

Associations of SSX2 with chemical compounds

• The SYT-SSX2 fusion transcripts were detected by a reverse transcription-polymerase chain reaction (RT-PCR) using RNA extracted from formalin-fixed, paraffin-embedded tissue [15].

Physical interactions of SSX2

• By performing glutathione-S-transferase pull-down assays, we found that both RAB3IP and SSX2IP interact directly with SSX2 in vitro [16].

Co-localisations of SSX2

• Likewise, the SSX2IP protein was found to be colocalizing with SSX2 in the nucleus [16].

Regulatory relationships of SSX2

• Seventy-two percent (13/18) of stage 4 NB expressed SSX-2 and 67% (12/18) expressed SSX-4 [17].

Other interactions of SSX2

• 2. The SSX1 and SSX2 genes encode closely related proteins (81% identity) of 188 amino acids that are rich in charged amino acids [1].
• Because SS18/SSX fusions do not seem to occur in other tumor types, and because synovial sarcomas may sometimes be difficult to distinguish from other spindle cell tumors, molecular genetic analysis has become established as an important diagnostic tool [18].
• However, coexpression of both RAB3IP and SSX2 led to colocalization of both proteins in the nucleus [16].
• The SSX gene family is composed of at least five functional and highly homologous members, SSX1 to SSX5, that are normally expressed in only the testis and thyroid [16].
• By fluorescence in situ hybridization, the marker chromosomes were shown to contain material from chromosomes X and 20, including the SSX gene cluster on the X chromosome and the SS18L1 gene, which shows strong homology with the SS18 gene, on chromosome 20 [18].

Analytical, diagnostic and therapeutic context of SSX2

• In a single histologically unremarkable monophasic SS, a slightly larger SYT-SSX2 RT-PCR product was observed [19].
• 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 [20].
• Analyzing patients with MM (n = 66) for antibody responses against MAGEA3, SSX2, and NY-ESO-1, we found strong antibody responses against CT antigens preferentially in patients who had received allogeneic stem cell transplantation (alloSCT) [21].
• RT-PCR analysis and sequence analysis demonstrated the presence of SS18/SSX2 fusion gene [22].
• Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients [11].

References