title: 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). TP53(R167H/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 TP53(R167H/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.forename: Jessica C
authors.initials: JC
authors.lastname: Sieren
authors.forename: David K
authors.initials: DK
authors.lastname: Meyerholz
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Wang
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Davis
authors.forename: John D
authors.initials: JD
authors.lastname: Newell
authors.forename: Emily
authors.initials: E
authors.lastname: Hammond
authors.forename: Judy A
authors.initials: JA
authors.lastname: Rohret
authors.forename: Frank A
authors.initials: FA
authors.lastname: Rohret
authors.forename: Jason T
authors.initials: JT
authors.lastname: Struzynski
authors.forename: J Adam
authors.initials: JA
authors.lastname: Goeken
authors.forename: Paul W
authors.initials: PW
authors.lastname: Naumann
authors.forename: Mariah R
authors.initials: MR
authors.lastname: Leidinger
authors.forename: Agshin
authors.initials: A
authors.lastname: Taghiyev
authors.forename: Richard
authors.initials: R
authors.lastname: Van Rheeden
authors.forename: Jussara
authors.initials: J
authors.lastname: Hagen
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Darbro
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Quelle
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Rogers
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D004195:Disease Models, Animal; D005260:Female; D011905:Genes, ras; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D013552:Swine; D014057:Tomography, X-Ray Computed; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53
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