{"doi":"10.26508/lsa.202101135","title":"UVB mutagenesis differs in <i>Nras</i>- and <i>Braf</i>-mutant mouse models of melanoma","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.","journal":"Life Science Alliance","year":2021,"id":174531,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260574,"name":"Rebecca C. Hennessey","orcid":"0000-0002-5283-6147","position":1,"is_corresponding":false},{"id":714718,"name":"Tirzah J. Weiss","orcid":null,"position":2,"is_corresponding":false},{"id":714075,"name":"David Tallman","orcid":"0000-0003-0089-6786","position":3,"is_corresponding":false},{"id":714719,"name":"Emma R. Crawford","orcid":null,"position":4,"is_corresponding":false},{"id":714076,"name":"Brandon Murphy","orcid":"0000-0002-5692-3643","position":5,"is_corresponding":false},{"id":380161,"name":"Amy Webb","orcid":"0000-0001-5503-7300","position":6,"is_corresponding":false},{"id":714720,"name":"Souhui Zhang","orcid":null,"position":7,"is_corresponding":false},{"id":714077,"name":"Krista M. D. La Perle","orcid":"0000-0002-6940-368X","position":8,"is_corresponding":false},{"id":404065,"name":"Craig J. Burd","orcid":"0000-0002-6899-6751","position":9,"is_corresponding":false},{"id":35287,"name":"Ross L. Levine","orcid":"0000-0002-7884-1905","position":10,"is_corresponding":false},{"id":255356,"name":"A. Hunter Shain","orcid":"0000-0002-2999-9706","position":11,"is_corresponding":false},{"id":233166,"name":"Christin E. Burd","orcid":"0000-0002-7919-3954","position":12,"is_corresponding":false},{"id":297426,"name":"Robert L. Bowman","orcid":"0000-0002-8294-8748","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-18T23:47:06.584146Z","pmid":"34210801","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}