This little piggy

Early identification and intervention greatly improves outcomes for patients with cancer. The development of many commonly used diagnostic techniques have been aided by animal models. While murine models of cancer have been very informative, their use for evaluation of surgical techniques and imaging tools is limited by their small size. Jessica Sieren, David Meyerholz, and colleagues at the University of Iowa developed a porcine model of cancer, in which animals express a variant of the tumor suppressor p53 (encoded by TP53) that is commonly found in human cancers. TP53R167H/R167H mutant pigs developed both lymphomas and bone-derived tumors, similar to patients with analogous mutations. Moreover, both computed tomography (CT), and magnetic resonance imaging (MRI) could be applied to follow tumoirgenesis in these animals. The TP53R167H/R167H mutant pig model provides a large animal cancer model that has potential to aid in development of non-invasive imaging techniques to aid in early cancer detection and diagnosis. The accompanying image is a false-colored 3 dimensional CD scan of the head of a TP53R167H/R167H mutant pig. The image reveals the development of an aggressive tumor (red) in the brain less than 3 months after a clear scan.

Published August 8, 2014, by Corinne Williams

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Development and translational imaging of a TP53 porcine tumorigenesis model
Jessica C. Sieren, … , Dawn E. Quelle, Christopher S. Rogers
Jessica C. Sieren, … , Dawn E. Quelle, Christopher S. Rogers
Published August 8, 2014
Citation Information: J Clin Invest. 2014;124(9):4052-4066. https://doi.org/10.1172/JCI75447.
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Technical Advance Oncology

Development and translational imaging of a TP53 porcine tumorigenesis model

Abstract

Cancer is the second deadliest disease in the United States, necessitating improvements in tumor diagnosis and treatment. Current model systems of cancer are informative, but translating promising imaging approaches and therapies to clinical practice has been challenging. In particular, the lack of a large-animal model that accurately mimics human cancer has been a major barrier to the development of effective diagnostic tools along with surgical and therapeutic interventions. Here, we developed a genetically modified porcine model of cancer in which animals express a mutation in TP53 (which encodes p53) that is orthologous to one commonly found in humans (R175H in people, R167H in pigs). TP53R167H/R167H mutant pigs primarily developed lymphomas and osteogenic tumors, recapitulating the tumor types observed in mice and humans expressing orthologous TP53 mutant alleles. CT and MRI imaging data effectively detected developing tumors, which were validated by histopathological evaluation after necropsy. Molecular genetic analyses confirmed that these animals expressed the R167H mutant p53, and evaluation of tumors revealed characteristic chromosomal instability. Together, these results demonstrated that TP53R167H/R167H pigs represent a large-animal tumor model that replicates the human condition. Our data further suggest that this model will be uniquely suited for developing clinically relevant, noninvasive imaging approaches to facilitate earlier detection, diagnosis, and treatment of human cancers.

Authors

Jessica C. Sieren, David K. Meyerholz, Xiao-Jun Wang, Bryan T. Davis, John D. Newell Jr., Emily Hammond, Judy A. Rohret, Frank A. Rohret, Jason T. Struzynski, J. Adam Goeken, Paul W. Naumann, Mariah R. Leidinger, Agshin Taghiyev, Richard Van Rheeden, Jussara Hagen, Benjamin W. Darbro, Dawn E. Quelle, Christopher S. Rogers

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