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Mol Oncol
2022 Oct 01;1619:3554-3567. doi: 10.1002/1878-0261.13301.
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Disruption of tp53 leads to cutaneous nevus and melanoma formation in Xenopus tropicalis.
Ran R
,
Li L
,
Shi Z
,
Liu G
,
Jiang H
,
Fang L
,
Xu T
,
Huang J
,
Chen W
,
Chen Y
.
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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 tp53Δ7/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.
ZDSYS20140509142721429 Shenzhen Key Laboratory of Cell Microenvironment, JCYJ20210324120205015 Shenzhen Science and Technology Program, 2017B030301018 Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research
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