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Disease models

Mouse model of intrahepatic cholangiocarcinoma (ICC)

Orthotopic allograft mouse models of ICC could be used to validate drivers of the disease. In mice, intrahepatic implantation of mouse liver progenitor cells expressing mutant forms of p53 and K-Ras (KRAS) caused development of tumors with histological features of ICC, including stromal cell infiltration. In the model, induced expression of a fusion gene containing Golgi-associated PDZ and coiled-coil motif containing (GOPCFIG) linked to c-ros proto-oncogene 1 receptor tyrosine kinase (ROS1), which has been found in a subset of patients with ICC, accelerated tumor growth. In the mouse model with established tumors that expressed the fusion gene, turning off its expression prevented further tumor growth. Next steps could include using the model to validate additional ICC targets.

SciBX 6(46); doi:10.1038/scibx.2013.1333
Published online Dec. 5, 2013

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Saborowski, A. et al. Proc. Natl. Acad. Sci. USA; published online Oct. 23, 2013;
Contact: Scott W. Lowe, Memorial Sloan-Kettering Cancer Center,
New York, N.Y.