The Fusion Oncogene FUS-CHOP Drives Sarcomagenesis of High-Grade Spindle Cell Sarcomas in Mice.
Mark ChenEric S XuNathan H LeisenringDiana M CardonaLixia LuoYan MaAndrea VenturaDavid G KirschPublished in: Sarcoma (2019)
Myxoid liposarcoma is a malignant soft tissue sarcoma characterized by a pathognomonic t(12;16)(q13;p11) translocation that produces a fusion oncoprotein, FUS-CHOP. This cancer is remarkably sensitive to radiotherapy and exhibits a unique pattern of extrapulmonary metastasis. Here, we report the generation and characterization of a spatially and temporally restricted mouse model of sarcoma driven by FUS-CHOP. Using different Cre drivers in the adipocyte lineage, we initiated in vivo tumorigenesis by expressing FUS-CHOP in Prrx1+ mesenchymal progenitor cells. In contrast, expression of FUS-CHOP in more differentiated cells does not form tumors in vivo, and early expression of the oncoprotein during embryogenesis is lethal. We also employ in vivo electroporation and CRISPR technology to rapidly generate spatially and temporally restricted mouse models of high-grade FUS-CHOP-driven sarcomas for preclinical studies.
Keyphrases
- high grade
- diffuse large b cell lymphoma
- mouse model
- low grade
- poor prognosis
- single cell
- adipose tissue
- magnetic resonance
- induced apoptosis
- crispr cas
- cell therapy
- early stage
- genome wide
- binding protein
- insulin resistance
- papillary thyroid
- gene expression
- squamous cell carcinoma
- genome editing
- long non coding rna
- radiation induced
- fatty acid
- contrast enhanced
- wild type
- pi k akt