Gene Expression Profile of Extraskeletal Myxoid Chondrosarcoma

Subbaya Subramanian, Robert B. West, Robert J. Marinelli, Torsten O. Nielsen, Brian P. Rubin, John R. Goldblum, Rajiv M. Patel, Shirley Zhu, Kelli Montgomery, Tony L. Ng, Christopher L. Corless, Michael C. Heinrich, and Matt van de Rijn

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  • Welcome to the web supplement to the paper:
    Gene Expression Profile of Extraskeletal Myxoid Chondrosarcoma published May, 2005 in Journal of Pathology 206. DOI: 10.1002/path.1792
  • Abstract:

    Extraskeletal myxoid chondrosarcoma (EMC) is a soft tissue tumor that occurs primarily in the extremities and is characterized by a balanced translocation most commonly involving t(9;22) (q22;q12). The morphological spectrum of EMC is broad and thus a diagnosis based on histology alone can be difficult. Currently, no systemic therapy exists that improves survival in EMC cases. We have performed gene expression profiling to discover new diagnostic markers and potential therapeutic targets. Global gene expression profiling of 10 EMC and 26 other sarcomas using 42,000 spot cDNA microarrays revealed that the cases of EMC were closely related to each other and distinct from the other tumors profiled. Significance analysis of microarrays (SAM) identified 86 genes that distinguished EMC from the other sarcomas with 0.25% likelihood of false significance. NMB, DKK1, DNER, CLCN3, and DEF6 were the top 5 genes in this analysis. In situ hybridization for NMB gene expression on tissue microarrays (TMAs) containing a total of 1,164 specimens representing 62 different sarcoma types and 15 different carcinoma types showed that NMB was highly expressed in 17 of 22 EMC cases and very rarely expressed in other tumors and thus could function as a novel diagnostic marker. High levels of expression of PPARG and its interacting protein PPARGC1A in most EMCs suggest activation of lipid metabolism pathways in this tumor. Small molecule inhibitors for PPARG exist and PPARG could be a potential therapeutic target for EMC.

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