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...

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Autores principales:	Jinxin Miao, Rong Li, Arnaud J Van Wettere, Haoran Guo, Alexandru-Flaviu Tabaran, M Gerald O'Sullivan, Timothy Carlson, Patricia M Scott, Kuisheng Chen, Dongling Gao, Huixiang Li, Yaohe Wang, Zhongde Wang, Robert T Cormier
Formato:	article
Lenguaje:	EN
Publicado:	Wolters Kluwer Medknow Publications 2021
Materias:	cancer hamsters tp53 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/85da8c116d8c450bb20e5263e01c9ebc
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spelling	oai:doaj.org-article:85da8c116d8c450bb20e5263e01c9ebc2021-11-12T10:17:19ZCancer spectrum in TP53-deficient golden Syrian hamsters: A new model for li-fraumeni syndrome1477-316310.4103/jcar.jcar_18_21https://doaj.org/article/85da8c116d8c450bb20e5263e01c9ebc2021-01-01T00:00:00Zhttp://www.carcinogenesis.com/article.asp?issn=1477-3163;year=2021;volume=20;issue=1;spage=18;epage=18;aulast=Miaohttps://doaj.org/toc/1477-3163Background: 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.Jinxin MiaoRong LiArnaud J Van WettereHaoran GuoAlexandru-Flaviu TabaranM Gerald O'SullivanTimothy CarlsonPatricia M ScottKuisheng ChenDongling GaoHuixiang LiYaohe WangZhongde WangRobert T CormierWolters Kluwer Medknow Publicationsarticlecancerhamsterstp53Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of Carcinogenesis, Vol 20, Iss 1, Pp 18-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer hamsters tp53 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cancer hamsters tp53 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jinxin Miao Rong Li Arnaud J Van Wettere Haoran Guo Alexandru-Flaviu Tabaran M Gerald O'Sullivan Timothy Carlson Patricia M Scott Kuisheng Chen Dongling Gao Huixiang Li Yaohe Wang Zhongde Wang Robert T Cormier Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for li-fraumeni syndrome
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	article
author	Jinxin Miao Rong Li Arnaud J Van Wettere Haoran Guo Alexandru-Flaviu Tabaran M Gerald O'Sullivan Timothy Carlson Patricia M Scott Kuisheng Chen Dongling Gao Huixiang Li Yaohe Wang Zhongde Wang Robert T Cormier
author_facet	Jinxin Miao Rong Li Arnaud J Van Wettere Haoran Guo Alexandru-Flaviu Tabaran M Gerald O'Sullivan Timothy Carlson Patricia M Scott Kuisheng Chen Dongling Gao Huixiang Li Yaohe Wang Zhongde Wang Robert T Cormier
author_sort	Jinxin Miao
title	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_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_sort	cancer spectrum in tp53-deficient golden syrian hamsters: a new model for li-fraumeni syndrome
publisher	Wolters Kluwer Medknow Publications
publishDate	2021
url	https://doaj.org/article/85da8c116d8c450bb20e5263e01c9ebc
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Cancer spectrum in TP53-deficient golden Syrian hamsters: A new model for li-fraumeni syndrome

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