Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for Li-Fraumeni syndrome.

Autor:	Miao J; Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, USA.; Sino-British Research Centre for Molecular Oncology, National Centre for International Research in Cell and Gene Therapy, Academy of Medical Sciences, Zhengzhou University, Henan, China.; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Henan, China., Li R; Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, USA., Wettere AJV; Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, USA., Guo H; Sino-British Research Centre for Molecular Oncology, National Centre for International Research in Cell and Gene Therapy, Academy of Medical Sciences, Zhengzhou University, Henan, China., Tabaran AF; College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.; Masonic Cancer Center, Comparative Pathology Shared Resource, University of Minnesota, Minneapolis, USA.; Department of Pathology, Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine Cluj-Napoca, Romania., O'Sullivan MG; College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.; Masonic Cancer Center, Comparative Pathology Shared Resource, University of Minnesota, Minneapolis, USA., Carlson T; College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.; Masonic Cancer Center, Comparative Pathology Shared Resource, University of Minnesota, Minneapolis, USA., Scott PM; Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN, USA., Chen K; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Gao D; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Li H; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Wang Y; Sino-British Research Centre for Molecular Oncology, National Centre for International Research in Cell and Gene Therapy, Academy of Medical Sciences, Zhengzhou University, Henan, China.; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University, London, UK., Wang Z; Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, USA., Cormier RT; Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN, USA.
Jazyk:	angličtina
Zdroj:	Journal of carcinogenesis [J Carcinog] 2021 Oct 07; Vol. 20, pp. 18. Date of Electronic Publication: 2021 Oct 07 (Print Publication: 2021).
DOI:	10.4103/jcar.jcar_18_21
Abstrakt:	Background: The TP53 tumor suppressor gene is the most commonly mutated gene in human cancers. Humans who inherit mutant TP53 alleles develop a wide range of early onset cancers, a disorder called Li-Fraumeni Syndrome (LFS). Trp53 -deficient mice recapitulate most but not all of the cancer phenotypes observed in TP53 -deficient human cancers, indicating that new animal models may complement current mouse models and better inform on human disease development. Materials and Methods: The recent application of CRISPR/Cas9 genetic engineering technology has permitted the emergence of golden Syrian hamsters as genetic models for wide range of diseases, including cancer. Here, the first cancer phenotype of TP53 knockout golden Syrian hamsters is described. Results: Hamsters that are homozygous for TP53 mutations become moribund on average ~ 139 days of age, while hamsters that are heterozygous become moribund at ~ 286 days. TP53 homozygous knockout hamsters develop a wide range of cancers, often synchronous and metastatic to multiple tissues, including lymphomas, several sarcomas, especially hemangiosarcomas, myeloid leukemias and several carcinomas. TP53 heterozygous mutants develop a more restricted tumor spectrum, primarily lymphomas. Conclusions: Overall, hamsters may provide insights into how TP53 deficiency leads to cancer in humans and can become a new model to test novel therapies. Competing Interests: There are no conflicts of interest. (Copyright: © 2021 Journal of Carcinogenesis.)
Databáze:	MEDLINE
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