J. Fernebro, P. Francis, P. Edén, Å. Borg, I. Panagopoulos, F. Mertens, J. Vallon-Christersson, M. Åkerman, N. Mandahl and M. Nilbert
Gene Expression Profiles Relate to SS18/SSX Fusion Type and Development of Metastasis in Synovial Sarcoma

We applied 27K spotted cDNA microarray slides to assess gene expression profiles in 26 samples from 24 patients with synovial sarcomas. The data were analyzed in relation to histopathologic type, gene fusion type, cytogenetic aberrations, and development of distant metastases. Supervised analysis based on gene fusion type in 12 synovial sarcomas with SS18/SSX1 and 9 with SS18/SSX2 revealed significant differences in gene expression profiles. Among the discriminating genes were signaling molecules and metallothioneins. When the 12 primary tumors that metastasized were compared to the 7 primary tumors from patients who remained free of metastasis, supervised analysis suggested differences in gene expression patterns also between these groups with an increased expression of e.g. topoisomerase type II alpha (TOP2A) and thymidylate synthetase (TYMS) in tumors that metastasized. Several of the discriminating genes have previously been found to be up-regulated in synovial sarcoma, albeit not correlated to gene fusion type or metastatic potential. Histopathology and degree of cytogenetic complexity did not significantly influence expression. Our findings suggest that the two major gene fusion variants, SS18/SSX1 and SS18/SSX2, result in different downstream effects. Also, a distinctive gene expression profile was detected among synovial sarcomas with a potential for metastasis, and such possible prognostic discriminators offers challenging possibilities to identify genetic markers that can be used to select high-risk patients for adjuvant chemotherapy.

LU TP 05-18