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The Fusion Oncogene FUS-CHOP Drives Sarcomagenesis of High-Grade Spindle Cell Sarcomas in Mice

Year: 2019
Type: article
Abstract: 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 initiatedin vivotumorigenesis by expressing FUS-CHOP inPrrx1+ mesenchymal progenitor cells. In contrast, expression of FUS-CHOP in more differentiated cells does not form tumorsin vivo, and early expression of the oncoprotein during embryogenesis is lethal. We also employin vivoelectroporation and CRISPR technology to rapidly generate spatially and temporally restricted mouse models of high-grade FUS-CHOP-driven sarcomas for preclinical studies.
Source: Sarcoma
DOI: 10.1155/2019/1340261
Authors: Mark Chen, Eric S. Xu, Nathan H. Leisenring, Diana M. Cardona, Lixia Luo, Yan Ma, Andrea Ventura, David G. Kirsch
Language: English
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $820
Funders: Geoffrey Beene Cancer Research Center, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, Duke Cancer Institute
Awards: G1174881085, Medical Scientist Training Program, G3420122323, G3829002440, G4433604574, G5043246103, G6666795512, G9000047122, G9000203772, Cancer Center Support Grant, Cancer Center Support Grant (CCSG)
OpenAlex ID: W2962858819
FWCI: 1.317
Cites: 46
Cited by: 15
Related to: 10