Results were compared to methylation data of 30 EwS with various EWSR1-ETS fusions and one EwS with FUS-ERG fusion, 16 URCS with CIC rearrangement and 10 URCS with BCOR alteration and a total of 81 EWSR1-associated soft tissue sarcomas including 7 angiomatoid fibrous histiocytomas, 7 clear cell sarcomas of the soft tissue, 28 desmoplastic small round cell tumors, 10 extraskeletal myxoid chondrosarcomas and 29 myxoid liposarcomas.
Fluorescence in situ hybridization (FISH) studies have shown involvement of the FUS gene in the majority of so-called hybrid LGFMS/SEF and in 10% to 25% of sarcomas with pure SEF morphology.
Overall, we provide a novel pathogenic mechanism of ALS associated with a FUS mutation under oxidative stress, as well as therapeutic insight regarding FUS pathology associated with excessive SGs.
Our findings therefore expand the spectrum of gene fusions that characterize LGFMS and suggest that the EWSR1 gene may substitute for the function of FUS in gene fusions of sarcoma.
This protein contains sequence similarities to TAR DNA-binding protein 43 (TDP-43) and fused-in-sarcoma (FUS) that are contained in cytoplasmic inclusions of ALS and FTLD-TDP or FTLD-FUS patients.
Low-grade fibromyxoid sarcoma is a rare soft tissue sarcoma of fibroblastic differentiation characterized by a deceptively benign morphologic appearance with almost consistent MUC4 expression and recurrent chromosomal translocations, t(7;16)(q34;p11) and t(11;16)(p11;p11), resulting in the FUS-CREB3L2 and FUS-CREB3L1 fusion genes, respectively.
In conclusion, this represents the first reported case of Ewing family tumors demonstrating a variant translocation involving FUS and FEV and highlights the need to consider alternative permutations of fusion partners for molecular diagnosis of sarcomas.
Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group.
The results of our study clearly show that expression of DOL54 is not only a characteristic feature of MLS with the FUS-DDIT3 chimera but that this is a frequent finding also in various other sarcomas.
The detection of fusion genes induced by tumor-specific translocations, such as EWS-FLI1 in Ewing's sarcoma, SYT-SSX in synovial sarcoma, and CHOP-FUS in myxoid liposarcoma, is becoming significant for clinical diagnosis, because these sarcomas are often indistinguishable from other bone and soft-tissue tumors.
The fusion genes found in sarcomas are dominated by the transcription factor type of genes with the TLS/FUS and EWS series of fusion genes as the largest group.
RBP56 has not previously been shown to be involved in tumorigenesis but it encodes a putative RNA-binding protein similar to the EWS and FUS (TLS) proteins known to play a pathogenetic role in several sarcomas.
The reciprocal translocation t(12;16)(q13;p11) has been shown to be highly characteristic of myxoid and round cell subtypes of liposarcoma, and the TLS/FUS-CHOP fusion gene that resulted from the translocation is expected to be a diagnostic molecular marker of these sarcomas.