{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T22:48:51Z","timestamp":1766011731272,"version":"3.48.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/10547\u20108"],"award-info":[{"award-number":["2017\/10547\u20108"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cutan Pathol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n \n The incidence of melanoma has been increasing in recent decades.\n BRAF<\/jats:italic>\n mutations appear in 50%\u201370% of melanomas. The BRAF\u2010targeted therapy increased the disease\u2010free survival of patients with metastatic melanoma, but this response may be short, due to several resistance mechanisms, such as the presence of other subclones with mutations. Evaluation of mutations and heterogeneity in the coding region of the\n BRAF<\/jats:italic>\n ,\n MAP2K1<\/jats:italic>\n , and\n MAP2K2<\/jats:italic>\n genes in primary and metastatic melanomas.\n <\/jats:p>\n <\/jats:sec>\n \n Patients and Methods<\/jats:title>\n \n Twenty\u2010seven samples of primary and metastatic superficial spreading melanoma (SSM) and acral lentiginous melanoma (ALM) were analyzed for\n BRAF<\/jats:italic>\n ,\n MAP2K1<\/jats:italic>\n , and\n MAP2K2<\/jats:italic>\n mutations using the next\u2010generation sequencing technique.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In ALM, the mutation rate found was 50% in the\n BRAF<\/jats:italic>\n and\n MAP2K1<\/jats:italic>\n genes and 28.6% in\n MAP2K2<\/jats:italic>\n . In the SSM,\n BRAF<\/jats:italic>\n was mutated in 76.9%,\n MAP2K1<\/jats:italic>\n in 30.8%, and\n MAP2K2<\/jats:italic>\n in 23.2% of the cases. All samples were formed by distinct tumor subclones in the same lesion. Intertumoral heterogeneity was present between primary and metastatic lesions of ALM in\n BRAF<\/jats:italic>\n ,\n MAP2K1<\/jats:italic>\n , and\n MAP2K2<\/jats:italic>\n ; the cases of SSM were heterogeneous for\n BRAF<\/jats:italic>\n and\n MAP2K1<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n We sought to evaluate the mutations in the BRAF, MAP2K1, and MAP2K2 genes, revealing a heterogeneous mutation profile in samples of ALM and SSM.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cup.14738","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T06:08:16Z","timestamp":1732601296000},"page":"48-59","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Heterogeneity in the Coding Region of\n \n BRAF<\/i>\n <\/scp>\n ,\n \n MAP2K1<\/i>\n <\/scp>\n , and\n \n MAP2K2<\/i>\n <\/scp>\n Genes in Primary and Metastatic Melanomas"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6208-0179","authenticated-orcid":false,"given":"Mariana","family":"Fernandes","sequence":"first","affiliation":[{"name":"Departament of Pathology Federal University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Barcelos","sequence":"additional","affiliation":[{"name":"Departament of Pathology Federal University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Cintra Lopes","family":"Carapeto","sequence":"additional","affiliation":[{"name":"Departament of Pathology Federal University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9673-4030","authenticated-orcid":false,"given":"Leonardo","family":"Cardili","sequence":"additional","affiliation":[{"name":"Departament of Pathology Federal University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreia Neves","family":"Comodo","sequence":"additional","affiliation":[{"name":"Departament of Pathology Federal University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana Fares","family":"Mazloum","sequence":"additional","affiliation":[{"name":"Departament of Pathology Federal University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryana Mara","family":"Marins","sequence":"additional","affiliation":[{"name":"Departament of Biophysics Federal University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agatha Ribeiro","family":"Mendes","sequence":"additional","affiliation":[{"name":"Departament of Biophysics Federal University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Bosco","family":"Pesquero","sequence":"additional","affiliation":[{"name":"Departament of Biophysics Federal University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles","family":"Landman","sequence":"additional","affiliation":[{"name":"Departament of Pathology Federal University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050092"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2019.09.017"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2019-0561-RA"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2011.03.005"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00766"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00215-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.4.10.2026"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2009.04.001"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0836"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0171-x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3233\/CBM-2011-0164"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23833.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5213"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11040465"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1026"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-3-8"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S39096"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.5772\/53629"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2019.02.002"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0642"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-397927-8.00011-7"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235122"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000000635"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000001418"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000001475"},{"key":"e_1_2_8_27_1","unstructured":"\u201cCOSMIC \u201daccessed April 10 2014 http:\/\/cancer.sanger.ac.uk\/cancergenome\/projects\/cosmic\/."},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.10.002"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.03.004"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23220"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2447"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2010.10185.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.526"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4333"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2017.09.007"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111153"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605912"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2017.05.015"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-3382"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3016"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13977"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.08.051"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800992"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2014.06.004"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1512"}],"container-title":["Journal of Cutaneous Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cup.14738","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T22:43:33Z","timestamp":1766011413000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cup.14738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,26]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/cup.14738"],"URL":"https:\/\/doi.org\/10.1111\/cup.14738","archive":["Portico"],"relation":{},"ISSN":["0303-6987","1600-0560"],"issn-type":[{"type":"print","value":"0303-6987"},{"type":"electronic","value":"1600-0560"}],"subject":[],"published":{"date-parts":[[2024,11,26]]},"assertion":[{"value":"2024-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}