Abstract LB-162: Translational imaging of tumorigenesis in a TP53 porcine cancer model

Abstract

Abstract Cancer remains the second deadliest disease in the United States, necessitating improvements in tumor diagnosis and treatment. Current model systems of cancer have been informative but also present challenges to translating promising imaging approaches and therapies to the clinic. The lack of a large animal model that accurately mimics human cancer has been a major barrier to the development of effective diagnostic tools and interventions (surgical and therapeutic). This study sought to 1) develop a genetically-modified porcine model of cancer expressing a TP53 mutation commonly found in humans (R175H in people, R167H in pigs), 2) validate the cellular p53 mutation and 3) evaluate tumor development in the animals using medical imaging, histopathology and molecular approaches. TP53R167H/R167H mutant pigs primarily developed lymphomas and osteogenic tumors, mimicking the tumor types observed in mice and humans expressing the orthologous TP53 mutant allele. CT and MRI imaging data effectively detected developing tumors, which were validated by histopathologic evaluation following necropsy. Molecular genetic analyses confirmed mutant p53 expression and characteristic chromosomal instability within the tumors. In conclusion, TP53R167H/R167H pigs provide a novel large animal tumor model that replicates the human condition and is uniquely suited to developing clinically-relevant, non-invasive imaging approaches to facilitate earlier detection, diagnosis and treatment of human cancers. Citation Format: Jessica C. Sieren, Xiao-Jun Wang, Bryan Davis, John D. Newell, Emily Hammond, Judy Rohret, Frank Rohret, Jason Struzynski, Adam Goeken, Paul Naumann, Mariah Leidinger, Jussara Hagen, Richard Van Rheeden, Benjamin W. Darbro, Dawn E. Quelle, David K. Meyerholz, Christopher S. Rogers. Translational imaging of tumorigenesis in a TP53 porcine cancer model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-162. doi:10.1158/1538-7445.AM2014-LB-162