Studies on the molecular pathogenesis of extraskeletal myxoid chondrosarcoma-cytogenetic, molecular genetic, and cDNA microarray analyses.

Extraskeletal myxoid chondrosarcomas (EMCs) are characterized by recurrent chromosome translocations resulting in fusions of the nuclear receptor TEC to various NH(2)-terminal partners. Here we describe the phenotypic, cytogenetic, and molecular genetic characteristics of a series of 10 EMCs. Using spectral karyotyping and fluorescence in situ hybridization, clonal chromosome abnormalities were detected in all but one tumor. A t(9;22)(q22;q12) translocation was found in three cases; a del(22)(q12-13)in one case; and variant translocations, including t(9;17)(q22;q11-12), t(7;9;17)(q32;q22;q11), and t(9;15)(q22;q21), were detected in one case each. Recurrent, secondary abnormalities, including trisomy 1q, 7, 8, 12, and 19, were found in seven tumors. All tumors contained translocation-generated or cryptic gene fusions, including EWS-TEC (five cases, of which one was a novel fusion), TAF2N-TEC (four cases), and TCF12-TEC (one case). cDNA microarray analysis of the gene expression patterns of two EMCs and a myxoid liposarcoma reference tumor revealed a remarkably distinct and uniform expression profile in both EMCs despite the fact that they had different histologies and expressed different fusion transcripts. The most differentially expressed gene in both tumors was CHI3L1, which encodes a secreted glycoprotein (YKL-40) previously implicated in various pathological conditions of extracellular matrix degradation as well as in cancer. Our findings suggests that EMC exhibits a tumor-specific gene expression profile, including overexpression of several cancer-related genes as well as genes implicated in chondrogenesis and neural-neuroendocrine differentiation, thus distinguishing it from other soft tissue sarcomas.