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Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for Li-Fraumeni syndrome
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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer - Medknow
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531574/ https://www.ncbi.nlm.nih.gov/pubmed/34729050 http://dx.doi.org/10.4103/jcar.jcar_18_21 |
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author | Miao, Jinxin Li, Rong Wettere, Arnaud J. Van Guo, Haoran Tabaran, Alexandru-Flaviu O'Sullivan, M. Gerald Carlson, Timothy Scott, Patricia M. Chen, Kuisheng Gao, Dongling Li, Huixiang Wang, Yaohe Wang, Zhongde Cormier, Robert T. |
author_facet | Miao, Jinxin Li, Rong Wettere, Arnaud J. Van Guo, Haoran Tabaran, Alexandru-Flaviu O'Sullivan, M. Gerald Carlson, Timothy Scott, Patricia M. Chen, Kuisheng Gao, Dongling Li, Huixiang Wang, Yaohe Wang, Zhongde Cormier, Robert T. |
author_sort | Miao, Jinxin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8531574 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Wolters Kluwer - Medknow |
record_format | MEDLINE/PubMed |
spelling | pubmed-85315742021-11-01 Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for Li-Fraumeni syndrome Miao, Jinxin Li, Rong Wettere, Arnaud J. Van Guo, Haoran Tabaran, Alexandru-Flaviu O'Sullivan, M. Gerald Carlson, Timothy Scott, Patricia M. Chen, Kuisheng Gao, Dongling Li, Huixiang Wang, Yaohe Wang, Zhongde Cormier, Robert T. J Carcinog Original Article 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. Wolters Kluwer - Medknow 2021-10-07 /pmc/articles/PMC8531574/ /pubmed/34729050 http://dx.doi.org/10.4103/jcar.jcar_18_21 Text en Copyright: © 2021 Journal of Carcinogenesis https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Miao, Jinxin Li, Rong Wettere, Arnaud J. Van Guo, Haoran Tabaran, Alexandru-Flaviu O'Sullivan, M. Gerald Carlson, Timothy Scott, Patricia M. Chen, Kuisheng Gao, Dongling Li, Huixiang Wang, Yaohe Wang, Zhongde Cormier, Robert T. Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for Li-Fraumeni syndrome |
title | Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for Li-Fraumeni syndrome |
title_full | Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for Li-Fraumeni syndrome |
title_fullStr | Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for Li-Fraumeni syndrome |
title_full_unstemmed | Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for Li-Fraumeni syndrome |
title_short | Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for Li-Fraumeni syndrome |
title_sort | cancer spectrum in tp53-deficient golden syrian hamsters: a new model for li-fraumeni syndrome |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531574/ https://www.ncbi.nlm.nih.gov/pubmed/34729050 http://dx.doi.org/10.4103/jcar.jcar_18_21 |
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