Saborowski, A., Saborowski, M., Davare, M. A., Druker, B. J., Klimstra, D. S., Lowe, S. W. (November 2013) Mouse model of intrahepatic cholangiocarcinoma validates FIG-ROS as a potent fusion oncogene and therapeutic target. Proceedings of the National Academy of Sciences of the United States of America, 110 (48). pp. 19513-19518. ISSN 00278424 (ISSN)
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Abstract
Cholangiocarcinoma is the second most common primary liver cancer and responds poorly to existing therapies. Intrahepatic cholangiocarcinoma (ICC) likely originates from the biliary tree and develops within the hepatic parenchyma. We have generated a flexible orthotopic allograft mouse model of ICC that incorporates common genetic alterations identified in human ICC and histologically resembles the human disease. We examined the utility of this model to validate driver alterations in ICC and tested their suitability as therapeutic targets. Specifically, we showed that the fused-in-glioblastoma-c- ros-oncogene1 (FIG-ROS1(S); FIG- ROS) fusion gene dramatically accelerates ICC development and that its inactivation in established tumors has a potent antitumor effect. Our studies establish a versatile model of ICC that will be a useful preclinical tool and validate ROS1 fusions as potent oncoproteins and therapeutic targets in ICC and potentially other tumor types.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types diseases & disorders > cancer > cancer types > liver cancer organism description > model organism organism description > animal > mammal > rodent > mouse bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene |
| CSHL Authors: | |
| Communities: | CSHL labs > Lowe lab |
| Depositing User: | Matt Covey |
| Date: | November 2013 |
| Date Deposited: | 23 Dec 2013 19:28 |
| Last Modified: | 20 Dec 2017 21:58 |
| PMCID: | PMC3845141 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/29173 |
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