MDM2 amplification in well- and dedifferentiated liposarcoma, FUS/EWSR1-DDIT3 gene fusions in myxoid liposarcoma, RB1 loss in spindle cell/pleomorphic lipoma).
These include MDM2 and CDK4 amplification in well-differentiated and dedifferentiated liposarcomas as well as FUS-DDIT3 rearrangements in myxoid liposarcoma.
The identification of signature cytogenetic and molecular alterations for certain lesions, such as PLAG1 gene rearrangement in lipoblastoma and FUS-DDIT3 fusion in myxoid liposarcoma, has been helpful in approaching these neoplasms and aiding in confirming the diagnosis.
Identification of inhibitors regulating cell proliferation and FUS-DDIT3 expression in myxoid liposarcoma using combined DNA, mRNA, and protein analyses.
Prior studies of lipoblastoma-like tumor have evaluated PLAG1, HMGA2, and RB1 immunohistochemistry and DDIT3 rearrangement status, with results supporting its distinction from lipoblastoma and myxoid liposarcoma.
This fusion gene as a hallmark of MLPS is very useful for differential diagnosis from other soft tissue sarcomas, and the associated protein, FUS-DDIT3, performs an important role in the phenotypic selection of targeted multipotent mesenchymal cells during oncogenesis.
We here investigate the functional role of FUS-DDIT3 in IGF-IR/PI3K/Akt signaling driving myxoid liposarcoma pathogenesis.<b>Experimental Design:</b> Immunohistochemical evaluation of key effectors of the IGF-IR/PI3K/Akt signaling axis was performed in a comprehensive cohort of myxoid liposarcoma specimens.
Here we studied a subgroup of sarcomas and leukaemias characterized by the FET (FUS, EWSR1, TAF15) family of fusion oncogenes, including FUS-DDIT3 in myxoid liposarcoma (MLS).
Phase II study of amrubicin (SM-5887), a synthetic 9-aminoanthracycline, as first line treatment in patients with metastatic or unresectable soft tissue sarcoma: durable response in myxoid liposarcoma with TLS-CHOP translocation.
We present 2 cases of liposarcoma arising in the vulva: a myxoid liposarcoma harboring DDIT3 and FUS rearrangements and a well differentiated liposarcoma/atypical lipomatous tumor harboring MDM2 amplification detected by fluorescence in situ hybridization.
To elucidate the mechanisms behind the high sensitivity of myxoid/round cell liposarcoma (MRCL) to trabectedin and the suggested selectivity for specific subtypes, we have developed and characterized three MRCL xenografts, namely ML017, ML015 and ML004 differing for the break point of the fusion gene FUS-CHOP, respectively of type I, II and III.
Myxoid/round-cell liposarcoma (MLS/RCLS) is characterized by either the fusion gene FUS-DDIT3 or the less commonly occurring EWSR1-DDIT3 and most cases carry few or no additional cytogenetic changes.
Translocated in liposarcoma-CCAAT/enhancer binding protein homologous protein (TLS-CHOP) (also known as FUS-DDIT3) chimeric oncoprotein is found in the majority of human myxoid liposarcoma (MLS), but its molecular function remains unclear.
Reporter assays showed that the EWSR1-DDIT3myxoid liposarcoma fusion protein, but not its wild-type counterparts EWSR1 and DDIT3, selectively repressed the transcriptional activity of cell lineage-specific marker genes in multipotent mesenchymal C3H10T1/2 cells.
Emerging phase 1 and 2 clinical data have shown high response rates in myxoid liposarcoma in part owing to the inhibition of the FUS-CHOP transcription factor.
Chromosomal translocations of t(12,16) (q13;p11) and t(12;22) (q13;q12), rendering gene fusions of DDIT3 (previously CHOP) with FUS and EWSR1, have been found to be characteristic of myxoid liposarcoma, and were identifiable in more than 95% cases.