Apart from the canonical SS18-SSX fusion, this is only the second alternative gene fusion variant described in synovial sarcoma to date, in addition to two cases harboring the SS18L1-SSX1 fusion.
The demonstration of characteristic sequences at the SYT-SSX breakpoint regions is expected to improve our understanding of the molecular genetic mechanisms behind translocations in general, and of the SYT-SSX fusions in synovial sarcoma in particular.
A characteristic SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas, a malignant soft tissue tumor widely believed to originate from as yet unidentified pluripotent stem cells.
This finding suggests that this novel fusion gene, which involves exon 6 of SSX only, is sufficient to keep the transforming function conferred by the SYT/SSX translocation of SS.
This involved blind analysis of two negative sarcoma samples and three synovial sarcomas in which corresponding frozen material had been previously shown to have the translocation involving different SSX genes.
In conclusion, the SYT-SSX fusion type is not a significant prognostic factor unlike tumor size, followed by histological grade for patients with localized synovial sarcoma in Japan.
Sequence analysis revealed that one of these antigens, HOM-MEL-40, was coded for by the SSX2 gene, which has recently been described to be involved in the t(X;18) translocation of human synovial sarcomas.
All analyzed cases showed the presence of SYT-SSX gene fusion transcripts confirming the diagnosis of SS, 10 carried the SYT-SSX1 fusion, and 2 the SYT-SSX2.
The majority of synovial sarcomas harbor a specific chromosomal translocation in which the proximal portion of the SYT gene at chromosome 18q11 is fused to the distal portion of one of several duplicated SSX genes (most notably SSX1 and SSX2) at chromosome Xp11.
The presence of an SYT-SSX gene fusion resulting from the t(X;18) characteristic of synovial sarcoma was demonstrated by reverse transcriptase polymerase chain reaction in three of three tumors in which adequate RNA could be obtained from paraffin blocks.
This study may be valuable for understanding the pathogenic role and molecular mechanism of the fusion gene SYT-SSX in synovial sarcoma through the proposed genome-wide approach.
We demonstrate that BRD9 supports oncogenic mechanisms underlying the SS18-SSX fusion in synovial sarcoma and highlight targeted degradation of BRD9 as a potential therapeutic opportunity in this disease.