title: A novel type of SYT/SSX fusion: methodological and biological implications.
abstract: Synovial sarcoma (SS) is a rare soft-tissue tumor that affects children and young adults. It is characterized by the chromosomal translocation t(X;18)(p11.2;q11.2), which results in the fusion of the SYT gene on chromosome 18 with a SSX gene on chromosome X. In the majority of cases, SYT is fused to exon 5 of SSX1 (64%), SSX2 (36%), or, rarely, SSX4. A novel fusion transcript variant deriving from the fusion of SYT to exon 6 of SSX4 gene (SYT/SSX4v) was found coexpressed in one of the previously reported SYT/SSX4 cases. In the present investigation, we describe a new SS case that was previously shown to be negative for SYT/SSX1 and SYT/SSX2 expression by conventional reverse transcription polymerase chain reaction (RT-PCR) methods. By redesigning and optimizing the RT-PCR protocol, we were able to detect SYT/SSX4v as the sole fusion transcript expressed in this tumor sample. 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. In about 3% of morphologically, ultrastructurally, and immunohistochemically defined SS, the SYT/SSX fusion transcript is not detected using conventional RT-PCR. Here we demonstrate that optimization of the RT-PCR method is important for detecting different and unexpected SYT/SSX variants, which otherwise could be overlooked. Using nine cases of SS in which SYT/SSX fusion transcripts were not detected by conventional RT-PCR methods, we demonstrate the presence of SYT/SSX transcripts in two cases using the proposed RT-PCR approach. Applications of optimized RT-PCR can contribute to reduce false-negative SYT/SSX SS cases reported in literature.
authors.affiliation: Department of Cellular and Molecular Tumor Pathology, Cancer Centrum Karolinska, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Törnkvist
authors.forename: Bertha
authors.initials: B
authors.lastname: Brodin
authors.forename: Armando
authors.initials: A
authors.lastname: Bartolazzi
authors.forename: Olle
authors.initials: O
authors.lastname: Larsson
mesh_terms: D000328:Adult; D001483:Base Sequence; D003001:Cloning, Molecular / Q000379:methods; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000032:analysis; D013584:Sarcoma, Synovial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017422:Sequence Analysis, DNA; D014746:Vimentin / Q000032:analysis
chemical_list: D018076:DNA, Complementary; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm; D009418:S100 Proteins; C116512:SYT-SSX fusion protein; D014746:Vimentin; D007633:Keratins