Mouse model of intrahepatic cholangiocarcinoma validates FIG-ROS as a potent fusion oncogene and therapeutic target

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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URL: http://www.ncbi.nlm.nih.gov/pubmed/24154728
DOI: 10.1073/pnas.1311707110

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: http://repository.cshl.edu/id/eprint/29173

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