{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:13:33Z","timestamp":1792034013988,"version":"4.4.0"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T00:00:00Z","timestamp":1624060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["21073"],"award-info":[{"award-number":["21073"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Deep penetrating nevi (DPNs) are rare melanocytic neoplasms consisting of pigmented spindled or epithelioid melanocytes with a distinctive wedge-shaped configuration showing activation of the WNT pathway, with unusual cyto-architectural features. It is unclear whether they show a distinct genomic profile associated with a diverse metastatic potential. We describe herein a cohort of 21 atypical DPNs analyzed by next-generation sequencing using the Ion AmpliSeq\u2122 Comprehensive Cancer Panel. We found that \u03b2-catenin exon 3 was mutated in 95% and MAP kinase pathway genes in 71% of the cases. Less frequent mutations were observed in HRAS (19%) and MAP2K1 (24%). Isocitrate dehydrogenases 1 (IDH1) mutations, including R132C, V178I, and S278L, were identified in 38% of cases and co-existed with BRAF\/HRAS mutations. The only case with progressive nodal disease carried alterations in the \u03b2-catenin pathway and mutations in IDH1 and NRAS (codon 61). By a comprehensive mutation analysis, we found low genetic heterogeneity and a lack of significant associations between specific gene mutations and histopathological features, despite atypical features. Whether the acquisition of an NRAS or IDH1 mutation in an atypical DPN may represent a molecular evolution implying a pathway to melanoma progression should be confirmed in a larger series.<\/jats:p>","DOI":"10.3390\/cancers13123066","type":"journal-article","created":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T22:00:02Z","timestamp":1624226402000},"page":"3066","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["NGS-Based Analysis of Atypical Deep Penetrating Nevi"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-1541","authenticated-orcid":false,"given":"Antonella","family":"Manca","sequence":"first","affiliation":[{"name":"Institute of Genetic & Biomedical Research, National Research Council, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Sini","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche (CNR), 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Cesinaro","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliero Universitaria Policlinico Modena, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3325-2357","authenticated-orcid":false,"given":"Francesca","family":"Portelli","sequence":"additional","affiliation":[{"name":"Section of Pathological Anatomy, Department of Health Sciences, University of Florence, 50121 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-2917","authenticated-orcid":false,"given":"Carmelo","family":"Urso","sequence":"additional","affiliation":[{"name":"Dermatopathology Study Center of Florence, 50129 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5797-1073","authenticated-orcid":false,"given":"Maria","family":"Lentini","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Cardia","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llucia","family":"Alos","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednic de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Cook","sequence":"additional","affiliation":[{"name":"Division of Pathology, University of Surrey, Guildford GU2 7XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6145-8275","authenticated-orcid":false,"given":"Sara","family":"Simi","sequence":"additional","affiliation":[{"name":"Section of Pathological Anatomy, Department of Health Sciences, University of Florence, 50121 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-6056","authenticated-orcid":false,"given":"Panagiotis","family":"Paliogiannis","sequence":"additional","affiliation":[{"name":"Laboratory Quality Control Unit, University Hospital (AOU) of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6531-7998","authenticated-orcid":false,"given":"Vincenzo","family":"De Giorgi","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Azienda USL Toscana Centro, 50122 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cossu","sequence":"additional","affiliation":[{"name":"Department of Medical Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4350-2276","authenticated-orcid":false,"given":"Giuseppe","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Massi","sequence":"additional","affiliation":[{"name":"Section of Pathological Anatomy, Department of Health Sciences, University of Florence, 50121 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/00000478-198901000-00005","article-title":"Deep Penetrating Nevus","volume":"13","author":"Seab","year":"1989","journal-title":"Am. 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