© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 11, 974-975,
June 2, 1999
© 1999 Oxford University Press
CORRESPONDENCE |
A Novel Fusion Gene, SYT-SSX4, in Synovial Sarcoma
Affiliation of authors: B. Skytting, Department of Orthopedics, Stockholm Soder Hospital, Sweden; G. Nilsson, Oncology Sevice, Department of Orthopedics and Cellular and Molecular Tumor Pathology, Karolinska Hospital, Stockholm, Sweden; B. Brodin, Y. Xie, O. Larsson, Cellular and Molecular Tumor Pathology, Karolinska Hospital; J. Lundeberg, M. Uhlén, Department of Biotechnology, Royal Institute of Technology (KTH), Stockholm.
Correspondence to: Olle Larsson, Ph.D., Cellular and Molecular Tumor Pathology, CCK, R8:04, Karolinska Hospital, SE-171 76 Stockholm, Sweden (e-mail: olle.larsson{at}onkpat.ki.se).
Cloning of the translocation t(X;18) (p11.2;q11.2) from human synovial sarcoma revealed a fusion between the SYT gene, also known as SSXT, located on chromosome 18 and the SSX gene located on the X chromosome (1). Five variants of the SSX gene (SSX1, SSX2, SSX3, SSX4, and SSX5) have been identified (2) but, to date, only SSX1 and SSX2 have been shown to fuse with the SYT gene in the translocation t(X;18) in synovial sarcoma (3,4).
We analyzed the type of SYT-SSX fusion messenger RNA in biopsy specimens from three
synovial sarcomas by nested reverse transcription-polymerase chain reaction (RT-PCR)
amplification. Two of the tumors were positive with either the SSX1 or the SSX2 primer, and
one was positive with both RT-PCR assays (Fig. 1, A-C)
. Sequence
analysis showed that the 5' end of the 581-base-pair (bp) amplicon of the biopsy
specimen in question contained a 187-bp fragment with 100% homology to the SYT gene
linked to a 246-bp fragment with 100% homology to the long splice variant of SSX4. The
breakpoint on SSX4 was identical to that observed for SSX1 and SSX2, in that all of the SSX
genes involved in the SYT-SSX fusion genes split between the fourth and the fifth exons, leaving
the fifth and sixth exons of the SSX variants to fuse with the 3' region of SYT.
|
The major differences in sequences among the three SSX variants are found in exon 5. The primers used for discriminating SSX1 from SSX2 recognize two different 21-bp sequences in this exon (Fig. 1, D)
. Analysis of the binding sites for the primers
revealed a difference of 4 bp for the SSX4 sequence compared with 5 bp for SSX2 by use of an
SSX1-reverse primer. With an SSX2-reverse primer, there was a mismatch of 4 bp for primer
binding to SSX4 and 5 bp for binding to SSX1. Since both SSX1 and SSX2 primers recognized
the SSX4 complementary DNA sequence, this recognition indicates that the difference at the four
positions is not enough to discriminate SSX4 from SSX1 or SSX2. Template mismatch with T as
the 3' terminal base has been reported previously (5). In a
majority of specimens examined in previous studies (3,6,7), the type of
fusion gene analysis has been based on PCR without sequence analysis, suggesting that the
detection of the SYT-SSX4 fusion variant may have been underestimated.
Recent evidence (6) indicates the prognostic importance of the two
fusion gene variants SYT-SSX1 and SYT-SSX2 in synovial sarcoma. This evidence suggests
that the base-pair differences between the SSX transcripts may have biologic significance. It is
tempting to speculate that these deviations may be localized to exon 5. In all three SYT-SSX
fusion variants, this domain contains several sites for phosphorylation. In SSX4, there are five
such residues (three serines and two threonines); in SSX1 and SSX2, there are five and six
residues, respectively (Fig. 1, E). Only two of these potential
phosphorylation sites are common for the three variants. As is also shown in Fig. 1, E, there is a potential site for SSX4-specific, N-linked glycosylation at the C-terminus
of the exon 5 domain. SSX1 contains two and SSX2 one N-linked glycosylation sites, one of
which is common between these two variants. These deviations may underlie the biologic
differences between them. Studies regarding the frequency of SYT-SSX4 and the potential
biologic differences between the fusion transcripts are under way.
NOTES
B. Skytting, G. Nilsson, B. Brodin, and Y. Xie all contributed equally to this letter.
We thank the Swedish Cancer Society, Cancer Society in Stockholm, and Lundbergs Research Foundation, Gothenburg, for their support.
REFERENCES
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2 Gure AO, Tureci O, Sahin U, Tsang S, Scanlan MJ, Jager E, et al. SSX: a multigene family with several members transcribed in normal testis and human cancer.Int J Cancer 1997;72:965-71.[CrossRef][Web of Science][Medline]cancerlit;98021352
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