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TLS-CHOP target gene DOL54 expression in liposarcomas and malignant fibrous histiocytomas
Hideharu Domoto1, Taisuke Hosaka, Kosuke Oikawa
1Department of Pathology, Tokyo Medical University, Tokyo, Japan.
Abstract:
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 DOL54 gene product is closely associated with adipogenic differentiation. DOL54 overexpression resulted in tumorigenicity when Chinese Hamster Ovary (CHO) cells were injected subcutaneously into nude mice. The biological significance of DOL54 expression for human malignant soft tissue tumors, however, has not yet been investigated. We examined TLS-CHOP and DOL54 expression in M-LPS/RC-LPS, well-differentiated liposarcoma and malignant fibrous histiocytoma (MFH), a tumor whose cellular origin has not been determined. We observed DOL54 expression in 50% of M-LPS/RC-LPS cases (in which TLS-CHOP was also expressed) and 33% of MFH cases, suggesting that a portion of MFH lesions may either derive from adipocytic precursor cells or have the potential to undergo adipogenic differentiation. In this manner, M-LPS/RC-LPS and MFH lesions may share tumorigenic characteristics, resulting from the unscheduled expression of DOL54.
Insights
The liposarcoma-associated fusion oncoprotein 54 (DOL54) gene is linked to tumor development in soft tissue cancers. DOL54 expression was found in myxoid liposarcoma/round cell liposarcoma and some malignant fibrous histiocytoma cases.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The DOL54 gene is a target of the TLS/FUS-CHOP oncogene and is involved in adipogenic differentiation.
- DOL54 overexpression in cells led to tumor formation in mice.
- The role of DOL54 in human soft tissue tumors remains unclear.
Purpose of the Study:
- To investigate the expression of TLS-CHOP and DOL54 in myxoid liposarcoma/round cell liposarcoma (M-LPS/RC-LPS), well-differentiated liposarcoma, and malignant fibrous histiocytoma (MFH).
- To explore the potential link between DOL54 expression and adipocytic differentiation in these tumors.
Main Methods:
- Immunohistochemical analysis of TLS-CHOP and DOL54 expression in patient tumor samples.
- Correlation of DOL54 expression with tumor type and differentiation status.
Main Results:
- DOL54 was expressed in 50% of M-LPS/RC-LPS cases, often co-expressed with TLS-CHOP.
- DOL54 expression was observed in 33% of MFH cases.
- Findings suggest MFH may originate from adipocytic precursors or undergo adipogenic differentiation.
Conclusions:
- Unscheduled DOL54 expression may contribute to tumorigenesis in both M-LPS/RC-LPS and MFH.
- A subset of MFH may share adipocytic origins or differentiation potential with liposarcomas.