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- W3174477462 endingPage "e202101135" @default.
- W3174477462 startingPage "e202101135" @default.
- W3174477462 abstract "BRAF-mutant melanomas are more likely than NRAS-mutant melanomas to arise in anatomical locations protected from chronic sun damage. We hypothesized that this discrepancy in tumor location is a consequence of the differential sensitivity of BRAF and NRAS-mutant melanocytes to ultraviolet light (UV)-mediated carcinogenesis. We tested this hypothesis by comparing the mutagenic consequences of a single neonatal, ultraviolet-AI (UVA; 340-400 nm) or ultraviolet-B (UVB; 280-390 nm) exposure in mouse models heterozygous for mutant Braf or homozygous for mutant Nras Tumor onset was accelerated by UVB, but not UVA, and the resulting melanomas contained recurrent mutations affecting the RING domain of MAP3K1 and Actin-binding domain of Filamin A. Melanomas from UVB-irradiated, Braf-mutant mice averaged twice as many single-nucleotide variants and five times as many dipyrimidine variants than tumors from similarly irradiated Nras-mutant mice. A mutational signature discovered in UVB-accelerated tumors mirrored COSMIC signatures associated with human skin cancer and was more prominent in Braf- than Nras-mutant murine melanomas. These data show that a single UVB exposure yields a greater burden of mutations in murine tumors driven by oncogenic Braf." @default.
- W3174477462 created "2021-07-05" @default.
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- W3174477462 date "2021-07-01" @default.
- W3174477462 modified "2023-10-16" @default.
- W3174477462 title "UVB mutagenesis differs in <i>Nras</i>- and <i>Braf</i>-mutant mouse models of melanoma" @default.
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- W3174477462 doi "https://doi.org/10.26508/lsa.202101135" @default.
- W3174477462 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8321651" @default.
- W3174477462 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34210801" @default.
- W3174477462 hasPublicationYear "2021" @default.
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