{"doi":"10.1002/ijc.35087","title":"Expanding the landscape of oncogenic drivers and treatment options in acral and mucosal melanomas by targeted genomic profiling","abstract":"Despite advancements in treating cutaneous melanoma, patients with acral and mucosal (A/M) melanomas still have limited therapeutic options and poor prognoses. We analyzed 156 melanomas (101 cutaneous, 28 acral, and 27 mucosal) using the Foundation One cancer-gene specific clinical testing platform and identified new, potentially targetable genomic alterations (GAs) in specific anatomic sites of A/M melanomas. Using novel pre-clinical models of A/M melanoma, we demonstrate that several GAs and corresponding oncogenic pathways associated with cutaneous melanomas are similarly targetable in A/M melanomas. Other alterations, including MYC and CRKL amplifications, were unique to A/M melanomas and susceptible to indirect targeting using the BRD4 inhibitor JQ1 or Src/ABL inhibitor dasatinib, respectively. We further identified new, actionable A/M-specific alterations, including an inactivating NF2 fusion in a mucosal melanoma responsive to dasatinib in vivo. Our study highlights new molecular differences between cutaneous and A/M melanomas, and across different anatomic sites within A/M, which may change clinical testing and treatment paradigms for these rare melanomas.","journal":"International Journal of Cancer","year":2024,"id":448939,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9454,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":575816,"name":"Robert J. Van Gulick","orcid":"0000-0002-6300-9569","position":1,"is_corresponding":false},{"id":455484,"name":"William A. Robinson","orcid":"0000-0003-1875-9691","position":2,"is_corresponding":false},{"id":574755,"name":"Tariq I. Mughal","orcid":"0000-0003-1005-7724","position":3,"is_corresponding":false},{"id":506822,"name":"Richard P. Tobin","orcid":"0000-0003-3890-4534","position":4,"is_corresponding":false},{"id":697904,"name":"Morgan MacBeth","orcid":"0000-0003-1299-0999","position":5,"is_corresponding":false},{"id":1267861,"name":"Blair Holman","orcid":"0009-0005-4224-0111","position":6,"is_corresponding":false},{"id":1268297,"name":"Anthony Classon","orcid":null,"position":7,"is_corresponding":false},{"id":394520,"name":"Stacey M. Bagby","orcid":"0009-0005-3355-3861","position":8,"is_corresponding":false},{"id":396076,"name":"Betelehem W. Yacob","orcid":null,"position":9,"is_corresponding":false},{"id":1184674,"name":"Sarah J. 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Ross","orcid":"0000-0001-5865-6828","position":19,"is_corresponding":false},{"id":394519,"name":"Todd M. Pitts","orcid":"0000-0002-8123-9894","position":20,"is_corresponding":false},{"id":530524,"name":"Matthew J. Rioth","orcid":"0000-0002-9605-3005","position":21,"is_corresponding":false},{"id":535325,"name":"Karl D. Lewis","orcid":"0000-0001-9893-0537","position":22,"is_corresponding":false},{"id":455483,"name":"Theresa Medina","orcid":"0000-0003-0579-4121","position":23,"is_corresponding":false},{"id":10993,"name":"Martin D. McCarter","orcid":"0000-0001-8174-1713","position":24,"is_corresponding":false},{"id":68940,"name":"René González","orcid":"0000-0002-7435-6208","position":25,"is_corresponding":false},{"id":575819,"name":"Kasey L. Couts","orcid":"0000-0002-2088-2229","position":26,"is_corresponding":false},{"id":876204,"name":"Jacqueline A. 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