Restriction fragment analysis showed that the CHOP gene and its flanking sequences were not rearranged in any of these tumor types, indicating that the 12q translocation breakpoints in pleomorphic adenoma and clear-cell sarcoma are different from that in myxoid liposarcoma.
The C/EBP-homologous transcription factor CHOP (GADD153) is inducible by growth inhibition or DNA damage, and has been shown to be oncogenically activated by the specific (12;16) translocation in human myxoid liposarcoma.
Thus, rearrangements of the CHOP gene appear to be specific for myxoid liposarcoma with t(12;16) and are not associated with lipoblastic differentiation.
Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases.
Downstream of the gene for the liposarcoma-associated fusion oncoprotein 54 (DOL54) is a target gene of the myxoid liposarcoma and round cell liposarcoma (M-LPS/RC-LPS) oncogene, TLS/FUS-CHOP.
The following case illustrates the utility of molecular cytogenetic and reverse transcriptase-polymerase chain reaction techniques in diagnosing an ins(22;12)(q12;q13q14) and associated EWS-CHOP fusion transcript in a myxoid/round cell liposarcoma exhibiting a der(16)t(1;16)(q11;q11).
The FUS gene at 16p11 fuses with DDIT3 and ATF1 as the result of translocations with chromosome band 12q13 in myxoid liposarcoma and angiomatoid fibrous histiocytoma, respectively, and with ERG as the result of a t(16;21)(p11;q22) in acute myeloid leukemia.
Described here is the use of detecting TLS/FUS-CHOP fusion transcripts to confirm the diagnosis of a myxoid liposarcoma by nested reverse transcription-polymerase chain reaction assay using archival formalin-fixed, paraffin-embedded tissues of a young man with a benign-looking myxoid tumor on his upper extremity, which is often misdiagnosed clinically or histopathologically as a benign tumor.
The DOL54 gene [also known as megakaryocyte stimulating factor, articular superficial zone protein (SZP) or proteoglycan 4 (PRG4)], was cloned as a downstream target gene of the FUS-DDIT3 chimera, which is the fusion gene that characterizes myxoid liposarcoma (MLS).
The present data show that the epithelioid variant of pleomorphic liposarcoma represents a further variant of myxoid liposarcoma sharing the FUS-CHOP fusion transcript but carrying a distinct expression profile, in keeping with its aggressive clinical course.
C/EBPzeta, also known as GADD153, CHOP10, and DDIT3 has been found associated with the development of myxoid liposarcoma and the progression of melanoma.
The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells.
Taken together, our observations suggest that expression of FUS-CHOP may be the initiating event in myxoid liposarcoma pathogenesis, and that MPCs may constitute one cell type from which these tumors originate.