1998 SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma
- 格式：pdf
- 大小：288.30 KB
- 文档页数：8
Volume 338Number 3
ؒ
153
SYT–SSX
GENE FUSION AS A DETERMINANT OF MORPHOLOGY AND PROGNOSIS IN SYNOVIAL SARCOMA
SYT–SSX
GENE FUSION AS A DETERMINANT OF MORPHOLOGY AND PROGNOSIS IN SYNOVIAL SARCOMA
A
KIRA
K
AWAI
, M.D., P
H
.D., J
AMES
W
OODRUFF
, M.D., J
OHN
H. H
EALEY
, M.D., M
URRAY
F. B
RENNAN
, M.D., C
RISTINA
R. A
NTONESCU
, M.D.,
AND
M
ARC
L
ADANYI
, M.D.
A
BSTRACT
Background
Synovial sarcomas account for up to10 percent of soft-tissue sarcomas and include twomajor histologic subtypes, biphasic and monopha-sic, defined respectively by the presence and ab-sence of glandular epithelial differentiation in abackground of spindle tumor cells. A characteristic
SYT–SSX
fusion gene resulting from the chromoso-mal translocation t(X;18)(p11;q11) is detectable in al-most all synovial sarcomas. The translocation fusesthe
SYT
gene from chromosome 18 to either of twohighly homologous genes at Xp11,
SSX1
or
SSX2.SYT–SSX1
and
SYT–SSX2
are thought to function asaberrant transcriptional regulators. We attempted todetermine the influence of the two alternative formsof the
SYT–SSX
fusion gene on tumor morphologyand clinical outcome in patients with this sarcoma.
Methods
We analyzed
SYT–SSX
fusion transcriptsin 45 synovial sarcomas (33 monophasic and 12 bi-phasic) by the reverse-transcriptase polymerase chainreaction and compared the results with relevant clin-ical and pathological data.
Results
The
SYT–SSX1
and
SYT–SSX2
fusiontranscripts were detected in 29 (64 percent) and 16(36 percent) of the tumors, respectively. There was asignificant relation (P
ϭ
0.003) between histologicsubtype (monophasic vs. biphasic) and
SSX1
or
SSX2
involvement in the fusion transcript: all 12 bi-phasic synovial sarcomas had an
SYT–SSX1
fusiontranscript, and all 16 tumors that were positive for
SYT–SSX2
were monophasic. Kaplan–Meier analysisof 39 patients with localized tumors showed that the15 patients with
SYT–SSX2
had significantly bettermetastasis-free survival than the 24 patients with
SYT–SSX1
(P
ϭ
0.03 by multivariate analysis; relativerisk, 3.0). There were no significant correlations be-tween the type of
SYT–SSX
transcript and age, sex,tumor location and size, whether there were metas-tases at diagnosis, or whether patients underwentchemotherapy. Histologic subtype alone was notprognostically important.
Conclusions
The type of
SYT–SSX
fusion tran-script correlates with both the histologic subtypeand the clinical behavior of synovial sarcoma.
SYT–SSX
fusion transcripts are a defining diagnosticmarker of synovial sarcomas and may also yield im-portant independent prognostic information. (N EnglJ Med 1998;338:153-60.) ©1998, Massachusetts Medical Society.
From the Departments of Surgery (A.K., J.H.H., M.F.B.), Pathology(J.W., C.R.A., M.L.), and Human Genetics (M.L.), Memorial Sloan-Ket-tering Cancer Center, New York. Address reprint requests to Dr. Ladanyiat the Department of Pathology, Memorial Sloan-Kettering Cancer Center,1275 York Ave., New York, NY 10021.
YNOVIAL sarcomas, which account for 5 to10 percent of soft-tissue sarcomas, typicallyarise in the para-articular regions in adoles-cents and young adults. These tumors occurin two major forms, biphasic and monophasic.
1
Bi-phasic synovial sarcomas contain both epithelial cellsarranged in glandular structures and spindle cells,whereas monophasic types are entirely composed ofspindle cells.Cytogenetic studies of synovial sarcomas have re-vealed a characteristic chromosomal translocation,t(X;18)(p11;q11), in more than 90 percent of bothbiphasic and monophasic tumors.
2
The presence ofthis translocation as the sole cytogenetic abnormal-ity in at least some tumors suggests that it is theprimary causal event in synovial sarcoma. Cloning ofthe translocation breakpoints showed that t(X;18)results in the fusion of two novel genes, designated
SYT
(at 18q11) and
SSX
(at Xp11).
3
It soon be-came apparent that the Xp11 breakpoint actually in-volves either of two closely related genes,
SSX1
and
SSX2,
4,5
located in the vicinity of ornithine amino-transferase–like (OATL) pseudogenes 1 and 2, re-spectively. The
SSX1
and
SSX2
genes are presumablyderived from a relatively recent duplication eventand encode proteins with considerable homology(81 percent). Recently, additional related
SSX
genes,apparently not involved by t(X;18), have been iden-tified in Xp11.
6,7
Like other chromosomal translocations in sarco-mas, t(X;18) results in the formation of a chimericprotein that probably deregulates the transcriptionand, hence, the expression of specific target genes.
8,9
Consistent with the intracellular site of transcrip-tional regulators, SYT, SSX, and SYT–SSX are nucle-ar proteins.
