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.