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

First Author  Saborowski A Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  48 Pages  19513-8
PubMed ID  24154728 Mgi Jnum  J:202905
Mgi Id  MGI:5523361 Doi  10.1073/pnas.1311707110
Citation  Saborowski A, et al. (2013) Mouse model of intrahepatic cholangiocarcinoma validates FIG-ROS as a potent fusion oncogene and therapeutic target. Proc Natl Acad Sci U S A 110(48):19513-8
abstractText  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.
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