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Genome-wide Analysis of Gene Expression in Synovial Sarcomas Using a cDNA Microarray¹

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan [S. N., T. K., Yu. N.]; Laboratory for Medical Informatics, SNP Research Center, RIKEN (Institute of Physical and Chemical Research), Tokyo 108-8639, Japan [Tat. T.]; Department of Tissue Regeneration, Institute for Frontier Medical Sciences [S. N., T. H., J. T.], and Departments of Orthopaedic Surgery [T. H., To. N., Ta. N.], Pathology [Ya. N], and Surgery and Surgical Basic Science [S. N., M. I.], Graduate School of Medicine, College of Medical Technology [Tad. T.], Kyoto University, Kyoto 606-8507, Japan; Department of Orthopedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases [N. A.], Osaka 537-8511, Japan; Department of Orthopedic Surgery, Kyoto Prefectural University of Medicine [K. K.], Kyoto 602-0841, Japan

Among a histologically heterogeneous group of soft tissue sarcomas, synovial sarcoma (SS) is regarded as a "miscellaneous" entity of uncertain origin. Although recent molecular analysis has disclosed involvement of a specific chromosomal translocation in the pathogenesis of SS, its genetic features remain largely unclear. In the work reported here we examined genome-wide gene expression profiles of 13 SS cases and 34 other spindle-cell sarcoma cases by cDNA microarray consisting of 23,040 genes. A hierarchical clustering analysis grouped SS and malignant peripheral nerve sheath tumor into the same category, and these two types of tumor shared expression patterns of numerous genes relating to neural differentiation. Several genes were up-regulated in almost all SS cases, and the presumed functions of known genes among them were related to migration or differentiation of neural crest cells, suggesting the possibility of neuroectodermal origin of SS. Moreover, we identified a set of genes that divided SS cases into two putative subclasses, a feature that may shed light on novel biological aspects of SS in addition to those having to do with epithelial differentiation. These data have provided clues for understanding the origin and tumorigenesis of SS.

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