Disruption of tp53 leads to cutaneous nevus and melanoma formation in Xenopus tropicalis
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| Authors: | Rensen Ran Lanxin Li Zhaoying Shi Guanghui Liu Hao Jiang Liangchen Fang Tingting Xu Jixuan Huang Weiqi Chen Yonglong Chen |
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| Affiliation: | 1. School of Life Science and Technology, Harbin Institute of Technology, China ; 2. Department of Biology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, School of Life Sciences, Southern University of Science and Technology, Shenzhen China ; 3. School of Medical Technology and Engineering, Fujian Medical University, Fuzhou China |
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| Abstract: | In humans, germline TP53 mutations predispose carriers to a wide spectrum of cancers, which is known as Li–Fraumeni syndrome (LFS). To date, the association of melanomas with LFS remains unestablished. No melanomas have been reported in any P53‐modified mouse models either. In this study, we show that targeted disruption of P53 at the DNA‐binding domain in Xenopus tropicalis recapitulates LFS, with the formation of soft‐tissue sarcomas and pancreatic ductal adenocarcinoma. Interestingly, 19% of the 14‐month‐old tp53 Δ7/Δ7 homozygotes and 18% of tp53 +/Δ7 heterozygotes spontaneously developed small nevi and non‐invasive melanomas. Large invasive melanomas were also observed in other older homozygous mutants, with about 7.9% penetrance. Our data suggest that more dermatologic investigation of LFS patients should be able to settle the association of melanoma with LFS in epidemiology. Our model is also valuable for further investigation of the molecular mechanism underlying melanoma progression upon germline alteration of the tp53 locus. |
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| Keywords: | Li– Fraumeni syndrome, melanoma, nevi, tp53, Xenopus tropicalis |
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