In particular, class 4-6 semaphorins and axonal guidance cues endowed with pro-tumorigenic activity were more expressed in TAF15-NR4A3 tumors; vice versa, class 3 semaphorins, considered to convey growth inhibitory signals, were more abundant in EWSR1-NR4A3EMC.
Extraskeletal myxoid chondrosarcoma is characterized by the reciprocal chromosomal translocation t(9;22) and the resultant fused gene EWS RNA-binding protein 1 and nuclear receptor subfamily 4, group A, member 3 (EWSR1-NR4A3).
We have performed microarray analyses of these cells and identified several genes overexpressed in the presence of EWS/NR4A3 which are also overexpressed in EMC tumors.
NR4A3 rearrangement reliably distinguishes between the clinicopathologically overlapping entities myoepithelial carcinoma of soft tissue and cellular extraskeletal myxoid chondrosarcoma.
This is the first reported case of a remarkable soft tissue sarcoma that exhibits overlapping morphologic features between SS and EMC and that also harbors a combination of SS18-SSX2 and EWS-NR4A3 gene fusions.
Most, although not all, examples of EMC possess a unique balanced chromosomal translocation [t(9;22)(q22;q12)] between the EWSR1 and NR4A3 (previously termed TEC) genes.
These results suggest that the overall expression of PPARG in EMC may be regulated in part by the balance between EWSR1/NR4A3 and NR4A3, and that PPARG may play a crucial role in the development of these tumours.
These results suggest that the overall expression of PPARG in EMC may be regulated in part by the balance between EWSR1/NR4A3 and NR4A3, and that PPARG may play a crucial role in the development of these tumours.
Distinct chromosomal translocations have been identified in several myxoid sarcomas, including t(12;16)(q13;p11) FUS-DDIT3 in myxoid liposarcoma, t(7;16)(q34;p11) FUS-CREB3L2 in low-grade fibromyxoid sarcoma, and t(9;22)(q31;q12) EWSR1-NR4A3 in extraskeletal myxoid chondrosarcoma.
Chromosomal rearrangements involving 9q22, such as t(9;22)(q22;q12), and resultant NR4A3 fusion genes are tumor-type specific or pathognomotic for this entity and are assumed to play an important role in the development of EMC.
These results support the hypothesis that the role of EWS/NOR-1 in EMC may be to disrupt the proliferation properties of cells involved in chondrogenesis.
NOR-1 is normally involved in the balance between cell proliferation and cell death, and is implicated in oncogenesis as part of the EWS/NOR-1 fusion protein found in human extraskeletal myxoid chondrosarcoma (EMC) tumors.
Thus, RT-PCR detection of EWS-CHN or TAF2N-CHN fusion gene using archival paraffin-embedded tissue is a feasible and useful ancillary technique for the diagnosis of EMCS.
Genetic investigations showed the recently described novel translocation t(9;17)(q22;q11.2) and associated fusion of the CHN and RBP56 genes, contrasting with the translocation t(9;22)(q22;q12) and EWS/CHN gene fusion found in the majority of EMCs.