Chimeric Fusion Gene Analysis of Extraskeletal Myxoid Chondrosarcoma and its Pathologic Differential Diagnosis

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Extraskeletal myxoid chondrosarcoma (EMC) is known as a rare malignant soft tissue tumor. Recently, chromosomal rearrangements by the translocation, t(9;22), t(9;17), t(9;15), and t(3;9) have been identified in the many cases of EMC. These rearrangements result in gene fusions ; EWS-CHN, TAF2N-CHN, TCF12-CHN, and TFG-CHN. However, the function of fusion proteins is unknown. To examine the function of EWS-CHN fusion protein, we constructed an expression vector of EWS-CHN (pEC1.5). Several proteins in COS cells transfected with pEC1.5 were observed. To investigate the effect of fusion protein on the transcription, we performed luciferase reporter assay using the vector containing p21 promoter. The luciferase activity in COS cells transfected with pEC1.5 was lower than that of control. These results suggest that EWS-CHN fusion protein influences the expression level of some proteins, may be associated with p53 pathway and may exert oncogenic potential in EMC.We studied 22 cases of EMC by RT-PCR methods. EWS-CHN was detected in 10, TAF2N-CHN in 4 and TFG-CHN in one case. We identified novel EWS-CHN fusion junctions. We examined EWS or CHN gene rearrangement by FISH methods in five cases which were not able to detect a fusion gene by RT-PCR methods. We detected one EWS rearrangement and one CHN. However, there were no chimeric gene fusions in 15 cases of osteosarcoma, conventional chondrosarcoma and adenocarcinoma using by RT-PCR or FISH methods. These results suggest that these chimeric genes or gene rearrangements may be specific to EMC, and seem to be useful for pathologic diagnosis of EMC.