{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:43:03Z","timestamp":1785872583581,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:00Z","timestamp":1617753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009414","name":"Istituto Oncologico Veneto","doi-asserted-by":"publisher","award":["BIGID219MENI"],"award-info":[{"award-number":["BIGID219MENI"]}],"id":[{"id":"10.13039\/501100009414","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acral melanoma (AM) is a rare and aggressive subtype of melanoma affecting the palms, soles, and nail apparatus with similar incidence among different ethnicities. AM is unrelated to ultraviolet radiation and has a low mutation burden but frequent chromosomal rearrangements and gene amplifications. Next generation sequencing of 33 genes and somatic copy number variation (CNV) analysis with genome-wide single nucleotide polymorphism arrays were performed in order to molecularly characterize 48 primary AMs of Italian patients in association with clinicopathological and prognostic features. BRAF was the most commonly mutated gene, followed by NRAS and TP53, whereas TERT promoter, KIT, and ARID1A were less frequently mutated. Gains and losses were recurrently found in the 1q, 6p, 7, 8q, 20 and 22 chromosomes involving PREX2, RAC1, KMT2C, BRAF, CCND1, TERT, and AKT3 genes, and in the 6q, 9, 10, 11q and 16q chromosomes including CDKN2A, PTEN, and ADAMTS18 genes, respectively. This study confirmed the variety of gene mutations and the high load of CNV in primary AM. Some genomic alterations were associated with histologic prognostic features. BRAF mutations, found with a higher rate than previously reported, correlated with a low Breslow thickness, low mitotic count, low CNV of the AMs, and with early-stage of disease.<\/jats:p>","DOI":"10.3390\/ijms22083826","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T11:31:59Z","timestamp":1617795119000},"page":"3826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Molecular Landscape of Primary Acral Melanoma: A Multicenter Study of the Italian Melanoma Intergroup (IMI)"],"prefix":"10.3390","volume":"22","author":[{"given":"Lisa","family":"Elefanti","sequence":"first","affiliation":[{"name":"Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Zamuner","sequence":"additional","affiliation":[{"name":"Anatomy and Histology Unit, 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Rev. Pathol. Mech. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1111\/j.1365-2133.2011.10772.x","article-title":"Melanoma of the hand and foot: Epidemiological, prognostic and genetic features. A systematic review","volume":"166","author":"Durbec","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1111\/j.1755-148X.2011.00880.x","article-title":"The melanomas: A synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin","volume":"24","author":"Whiteman","year":"2011","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1046\/j.1365-2133.2000.03651.x","article-title":"Acral cutaneous melanoma in caucasians: Clinical features, histopathology and prognosis in 112 patients","volume":"143","author":"Kuchelmeister","year":"2000","journal-title":"Br. J. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1245\/s10434-013-3089-0","article-title":"Prognosis of Acral Melanoma: A Series of 281 Patients","volume":"20","author":"Bello","year":"2013","journal-title":"Ann. Surg. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5564","DOI":"10.1038\/s41598-017-05809-9","article-title":"A clinicopathological analysis of 153 acral melanomas and the relevance of mechanical stress","volume":"7","author":"Sheen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.2106\/00004623-199509000-00016","article-title":"Malignant melanoma of the foot and ankle","volume":"77","author":"Fortin","year":"1995","journal-title":"J. Bone Jt. Surg. Am. Vol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/00000658-199402000-00012","article-title":"Surgical Management and Prognostic Factors in Patients with Subungual Melanoma","volume":"219","author":"Heaton","year":"1994","journal-title":"Ann. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/978-3-319-22539-5_14","article-title":"Acral Lentiginous Melanoma","volume":"167","author":"Goydos","year":"2016","journal-title":"Cancer Treat. Res."},{"key":"ref_10","unstructured":"Elder, D.E., Massi, D., Scolyer, R.A., and Willemze, R. (2018). WHO Classification of Skin Tumours, IARC. [4th ed.]."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1001\/archdermatol.2008.609","article-title":"Acral Lentiginous Melanoma","volume":"145","author":"Bradford","year":"2009","journal-title":"Arch. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1111\/ced.13243","article-title":"Acral melanoma foot lesions. Part 1: Epidemiology, aetiology, and molecular pathology","volume":"42","author":"Desai","year":"2017","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cll.2011.03.005","article-title":"Acral Lentiginous Melanoma","volume":"31","author":"Piliang","year":"2011","journal-title":"Clin. Lab. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/pcmr.12885","article-title":"Acral lentiginous melanoma: Basic facts, biological characteristics and research perspectives of an understudied disease","volume":"34","author":"Adams","year":"2021","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-18988-3","article-title":"Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity","volume":"11","author":"Newell","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1093\/jnci\/djz005","article-title":"Targeted Genomic Profiling of Acral Melanoma","volume":"111","author":"Yeh","year":"2019","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/CMR.0000000000000222","article-title":"Molecular profiling, including TERT promoter mutations, of acral lentiginous melanomas","volume":"26","author":"Vazquez","year":"2016","journal-title":"Melanoma Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1056\/NEJMoa050092","article-title":"Distinct Sets of Genetic Alterations in Melanoma","volume":"353","author":"Curtin","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_19","first-page":"175","article-title":"Whole-genome landscapes of major melanoma subtypes","volume":"545","author":"Hayward","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1101\/gr.213348.116","article-title":"Integrated genomic analyses reveal frequentTERTaberrations in acral melanoma","volume":"27","author":"Liang","year":"2017","journal-title":"Genome Res."},{"key":"ref_21","first-page":"502","article-title":"Melanoma genome sequencing reveals frequent PREX2 mutations","volume":"485","author":"Berger","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_22","unstructured":"Shi, K., Zhang, B., Kong, B.Y., Zhang, Y., Igartua, C., Mohan, L.S., Quan, V.L., Panah, E., Isales, M.C., and Beaubier, N. (2019). Distinct Genomic Features in a Retrospective Cohort of Mucosal, Acral and Vulvovaginal Melanomas. J. Am. Acad. Dermatol., 0190."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ejca.2019.07.008","article-title":"Clinical and genetic analysis of melanomas arising in acral sites","volume":"119","author":"Zaremba","year":"2019","journal-title":"Eur. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Dika, E., Lambertini, M., Pellegrini, C., Veronesi, G., Melotti, B., Riefolo, M., Sperandi, F., Patrizi, A., Ricci, C., and Mussi, M. (2021). Cutaneous and Mucosal Melanomas of Uncommon Sites: Where Do We Stand Now?. J. Clin. Med., 10.","DOI":"10.3390\/jcm10030478"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jdermsci.2013.07.013","article-title":"KIT, NRAS, BRAF and PTEN mutations in a sample of Swedish patients with acral lentiginous melanoma","volume":"72","author":"Zebary","year":"2013","journal-title":"J. Dermatol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.18632\/oncotarget.27642","article-title":"Mutation profile of primary subungual melanomas in Caucasians","volume":"11","author":"Borkowska","year":"2020","journal-title":"Oncotarget"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1097\/CMR.0000000000000688","article-title":"Clinical and molecular features of subungual melanomas are site-specific and distinct from acral melanomas","volume":"30","author":"Holman","year":"2020","journal-title":"Melanoma Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3182","DOI":"10.1200\/JCO.2012.47.7836","article-title":"Imatinib for Melanomas Harboring Mutationally Activated or Amplified KIT Arising on Mucosal, Acral, and Chronically Sun-Damaged Skin","volume":"31","author":"Hodi","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/pcmr.12865","article-title":"Distinct genomic traits of acral and mucosal melanomas revealed by targeted mutational profiling","volume":"33","author":"Zou","year":"2020","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Dumaz, N., Jouenne, F., Delyon, J., Mourah, S., Bensussan, A., and Lebb\u00e9, C. (2019). Atypical BRAF and NRAS Mutations in Mucosal Melanoma. Cancers, 11.","DOI":"10.3390\/cancers11081133"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1158\/0008-5472.CAN-13-2625","article-title":"Loss of NF1 in Cutaneous Melanoma Is Associated with RAS Activation and MEK Dependence","volume":"74","author":"Nissan","year":"2014","journal-title":"Cancer Res."},{"key":"ref_32","first-page":"49","article-title":"Diagnostic significance and prognostic role of the ARID1A gene in cancer outcomes (Review)","volume":"2","author":"Pavlidou","year":"2020","journal-title":"World Acad. Sci. J."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"V\u00e1raljai, R., Horn, S., Sucker, A., Piercianek, D., Schmitt, V., Carpinteiro, A., Becker, K., Reifenberger, J., Roesch, A., and Felsberg, J. (2021). Integrative Genomic Analyses of Patient-Matched Intracranial and Extracranial Metastases Reveal a Novel Brain-Specific Landscape of Genetic Variants in Driver Genes of Malignant Melanoma. Cancers, 13.","DOI":"10.3390\/cancers13040731"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-53636-x","article-title":"A comprehensive evaluation of pathogenic mutations in primary cutaneous melanomas, including the identification of novel loss-of-function variants","volume":"9","author":"Ticha","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/pcmr.12279","article-title":"The mutational burden of acral melanoma revealed by whole-genome sequencing and comparative analysis","volume":"27","author":"Furney","year":"2014","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1056\/NEJMoa1502583","article-title":"The Genetic Evolution of Melanoma from Precursor Lesions","volume":"373","author":"Shain","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1172\/JCI134402","article-title":"Epigenetic driver mutations in ARID1A shape cancer immune phenotype and immunotherapy","volume":"130","author":"Li","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1126\/science.1230062","article-title":"TERT Promoter Mutations in Familial and Sporadic Melanoma","volume":"339","author":"Horn","year":"2013","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1126\/science.1229259","article-title":"Highly Recurrent TERT Promoter Mutations in Human Melanoma","volume":"339","author":"Huang","year":"2013","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/cup.12323","article-title":"TERT promoter mutation is uncommon in acral lentiginous melanoma","volume":"41","author":"Liau","year":"2014","journal-title":"J. Cutan. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1111\/pcmr.12500","article-title":"HighTERTpromoter mutation frequency in non-acral cutaneous metastatic melanoma","volume":"29","author":"Ekedahl","year":"2016","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"D941","DOI":"10.1093\/nar\/gky1015","article-title":"COSMIC: The Catalogue Of Somatic Mutations In Cancer","volume":"47","author":"Tate","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11912-018-0733-7","article-title":"Molecular Pathways in Melanomagenesis: What We Learned from Next-Generation Sequencing Approaches","volume":"20","author":"Palmieri","year":"2018","journal-title":"Curr. Oncol. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/jid.2014.366","article-title":"Beyond BRAF V600: Clinical Mutation Panel Testing by Next-Generation Sequencing in Advanced Melanoma","volume":"135","author":"Siroy","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.cell.2012.06.024","article-title":"A Landscape of Driver Mutations in Melanoma","volume":"150","author":"Hodis","year":"2012","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1080\/21541248.2016.1178366","article-title":"Interplay between PREX2 mutations and the PI3K pathway and its effect on epigenetic regulation of gene expression in NRAS-mutant melanoma","volume":"7","year":"2016","journal-title":"Small GTPases"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1126\/science.1173569","article-title":"Activation of the PI3K Pathway in Cancer Through Inhibition of PTEN by Exchange Factor P-REX2a","volume":"325","author":"Fine","year":"2009","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1042\/BST20160269","article-title":"P-Rex1 and P-Rex2 RacGEFs and cancer","volume":"45","author":"Srijakotre","year":"2017","journal-title":"Biochem. Soc. Trans."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S1470-2045(17)30438-2","article-title":"The TNM classification of malignant tumours\u2014towards common understanding and reasonable expectations","volume":"18","author":"Brierley","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/j.cell.2015.05.044","article-title":"Genomic Classification of Cutaneous Melanoma","volume":"161","author":"Akbani","year":"2015","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/pcmr.12459","article-title":"The genomic landscape of cutaneous melanoma","volume":"29","author":"Zhang","year":"2016","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_52","unstructured":"RCore Team (2020). A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/3826\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:11:59Z","timestamp":1760364719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/3826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,7]]},"references-count":52,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22083826"],"URL":"https:\/\/doi.org\/10.3390\/ijms22083826","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,7]]}}}