Affiliations of authors: V. Agus, E. Tamborini, A. Mezzelani, S. Pilotti (Laboratory of Molecular Diagnosis, Department of Pathology), M. A. Pierotti (Experimental Oncology Department), Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Correspondence to: Silvana Pilotti, M.D., Laboratory of Molecular Diagnosis, Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian, 1 20133 Milan, Italy (e-mail: pilotti{at}istitutotumori.mi.it).
Synovial sarcoma is characterized cytogenetically by the nonrandom translocation t(X;18) (p11.2q11.2), which generates the fusion of two genes, SYT on chromosome 18 and one of the SSXs on chromosome Xp11.2, where five highly homologous genes (SSX1 to SSX5) have been so far described. Three different types of translocation have been identified in synovial sarcoma, involving SSX1, SSX2, and SSX4. To date, in the literature, only three cases of SYTSSX4 have been reported, one by Skytting et al. (1), one by our group (2), and one by Brodin et al. (3).
Recently, our laboratory identified an additional case of SYTSSX4. After receiving written informed consent from the patient, we therefore analyzed the snap-frozen samples from the two synovial sarcomas, monophasic in subtype, by reverse transcriptionpolymerase chain reaction, specifically amplifying the SYTSSX4 chimeric transcript following the procedures of Skytting et al. (1) (Fig. 1, A).
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At the level of the amino acid sequence, this new variant retains the majority of the Krüppel associated box (KRAB)-like domain present in the 5` portion of the SSX gene (aa 20 to 83), a region thought to be involved in transcriptional repression activity. Although the SSX repression domain (SSXRD) located in the last 34 residues of the C-terminus of the protein also seems to be responsible for transcriptional repression (5), it is tempting to speculate that the KRAB-like-containing N-terminal portion of the SSX protein may affect the activity of the chimeric protein on transactivation of different target genes.
Since, to our knowledge, only one variant each of fusion transcripts from SYTSSX1 and SYTSSX2 has been described to date (6,7), strongly implying that the rearrangement involved in these cases is a constant and reproducible mechanism, the SYTSSX4 translocation seems to present a high break-point variability (three of four cases examined) despite its relatively low frequency. Thus, this correspondence contributes to a better estimation of the SYTSSX4 rearrangement frequency by the identification of a set of primers specific for each variant of the SYTSSX4 fusion transcript.
NOTES
M. A. Pierotti and S. Pilotti were senior co-authors.
Supported by grants from Ministero della Sanita, Ricerca Finalizzata 1998-ICS030.1/RF98.32- Italy, and by grant 420.198.122 from the Associazione Italiana per la Ricerca sul Cancro.
REFERENCES
1
Skytting B, Nilsson B, Brodin B, Xie Y, Lundeberg J, Uhlen M, et al. A novel fusion gene, SYTSSX4, in synovial sarcoma [letter]. J Natl Cancer Inst 1999;91:9745.
2 Mancuso T, Mezzelani A, Riva C, Fabbri A, Dal Bo L, Sampietro G, et al. Analysis of SYTSSX fusion transcripts and bcl-2 expression and phosphorylation status in synovial sarcoma. Lab Invest 2000;80:80513.[Medline]
3 Brodin B, Haslam K, Yang K, Bartolazzi A, Xie Y, Starborg M, et al. Cloning and characterization of spliced fusion transcript variants of synovial sarcoma: SYT/SSX4, SYT/SSX4v, and SYT/SSX2v. Possible regulatory role of the fusion gene product in wild type SYT expression. Gene 2001;268:17382.[Medline]
4 Clark J, Rocques PJ, Crew AJ, Gill S, Shipley J, Chan AM, et al. Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma. Nat Genet 1994;7:5028.[Medline]
5 Lim FL, Soulez M, Koczan D, Thiesen HJ, Knight JC. A KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas. Oncogene 1998;17:20138.[Medline]
6 Safar A, Wickert R, Nelson M, Neff JR, Bridge JA. Characterization of a variant SYT SSX1 synovial sarcoma fusion transcript. Diagn Mol Pathol 1998;7:2837.[Medline]
7 Fligman I, Lonardo F, Jhanwar SC, Gerald WL, Woodruff J, Ladanyi M. Molecular diagnosis of synovial sarcoma and characterization of a variant SYTSSX2 fusion transcript. Am J Pathol 1995;147:15929.[Abstract]
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