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Alliance"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:p><jats:italic>BRAF<\/jats:italic>-mutant melanomas are more likely than\n                            <jats:italic>NRAS<\/jats:italic>-mutant melanomas to arise in anatomical\n                        locations protected from chronic sun damage. We hypothesized that this\n                        discrepancy in tumor location is a consequence of the differential\n                        sensitivity of <jats:italic>BRAF<\/jats:italic> and\n                            <jats:italic>NRAS<\/jats:italic>-mutant melanocytes to ultraviolet light\n                        (UV)-mediated carcinogenesis. We tested this hypothesis by comparing the\n                        mutagenic consequences of a single neonatal, ultraviolet-AI (UVA; 340\u2013400\n                        nm) or ultraviolet-B (UVB; 280\u2013390 nm) exposure in mouse models heterozygous\n                        for mutant <jats:italic>Braf<\/jats:italic> or homozygous for mutant\n                            <jats:italic>Nras<\/jats:italic>. Tumor onset was accelerated by UVB, but\n                        not UVA, and the resulting melanomas contained recurrent mutations affecting\n                        the RING domain of MAP3K1 and Actin-binding domain of Filamin A. Melanomas\n                        from UVB-irradiated, <jats:italic>Braf<\/jats:italic>-mutant mice averaged\n                        twice as many single-nucleotide variants and five times as many dipyrimidine\n                        variants than tumors from similarly irradiated\n                            <jats:italic>Nras<\/jats:italic>-mutant mice. A mutational signature\n                        discovered in UVB-accelerated tumors mirrored COSMIC signatures associated\n                        with human skin cancer and was more prominent in\n                            <jats:italic>Braf<\/jats:italic>- than\n                        <jats:italic>Nras<\/jats:italic>-mutant murine melanomas. These data show\n                        that a single UVB exposure yields a greater burden of mutations in murine\n                        tumors driven by oncogenic Braf.<\/jats:p>","DOI":"10.26508\/lsa.202101135","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T03:58:43Z","timestamp":1625543923000},"page":"e202101135","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["UVB mutagenesis differs in <i>Nras<\/i>- and <i>Braf<\/i>-mutant mouse\n                        models of melanoma"],"prefix":"10.26508","volume":"4","author":[{"given":"Robert L","family":"Bowman","sequence":"first","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan\n                            Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca C","family":"Hennessey","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State\n                            University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tirzah J","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State\n                            University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Tallman","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State\n                            University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma R","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, The Ohio State University,\n                            Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon M","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State\n                            University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, The Ohio State\n                            University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State\n                            University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6940-368X","authenticated-orcid":true,"given":"Krista MD","family":"La Perle","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, The Ohio State\n                            University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig J","family":"Burd","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, The Ohio State University,\n                            Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross L","family":"Levine","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan\n                            Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Hunter","family":"Shain","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Helen Diller Family Comprehensive\n                            Cancer Center, University of California, San Francisco, San Francisco,\n                            CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7919-3954","authenticated-orcid":false,"given":"Christin E","family":"Burd","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State\n                            University, Columbus, OH, USA"},{"name":"Department of Molecular Genetics, The Ohio State University,\n                            Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"12380","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"2021070508453758000_4.9.e202101135.1","unstructured":"Alexandrov L (2020) Sigprofiler. 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