2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T884,The origins of cutaneous melanoma are often traced to visible precursor lesions (e.g., melanocytic naevi), but ∼2/3 melanomas arise from clinically normal skin with no precursor lesion. BRAF V600E drives both melanoma and naevus formation, but eruptive naevi syndromes and the disproportionate role early-life UV exposure plays in melanoma risk suggest the presence of a hidden field of oncogene-mutant melanocytes within clinically normal skin, which may represent an earlier step in tumourigenesis. We aimed to determine whether BRAF V600E-mutant melanocytes were commonly present in non-lesional skin from adults at high risk of melanoma. We examined BRAF V600E mutation in 97 histologically and clinically normal, non-lesional skin samples from a high-risk Australian melanoma cohort. The skin selected was adjacent to a naevus or a prior melanoma site, photodamaged skin proximal (∼5cm) from melanoma excision, and photoprotected skin distant from lesions, as well as a low-risk neonatal foreskin-derived melanoblasts. We used immunohistochemistry to locate BRAF V600E-mutant cells in histopathology sections, droplet digital PCR to determine the fractional abundance of BRAF V600E in whole skin, and single-cell RNA sequencing to confirm cells as melanocytes and detect their transcriptional programs. We identified BRAF V600E-mutant melanocytes in skin surrounding naevi and primary melanomas, even years after tumour excision. Fields of BRAF V600E-mutant melanocytes are commonly observed in the skin of patients at high risk for melanoma and are up to 20-fold more dense and 50% more frequent in tumour-adjacent skin. Field cells exhibit a gene expression profile characteristic of BRAF V600E-induced growth arrest, consistent with dormant yet genetically primed cells. There is a reservoir of oncogene-harbouring melanocytes in normal skin. Our observations challenge the prevailing notion that melanocyte expression of BRAF V600E is inherently tumourigenic. The presence of such fields suggests that the scope of melanoma detection and prevention efforts might be extended beyond visible lesions, to encompass potentially precancerous fields of driver-mutant cells.31:Tb99,Abstract Background The origins of cutaneous melanoma are often traced to visible precursor lesions (e.g., melanocytic naevi), but ∼2/3 melanomas arise from clinically normal skin with no precursor lesion. BRAF V600E drives both melanoma and naevus formation, but eruptive naevi syndromes and the disproportionate role early-life UV exposure plays in melanoma risk suggest the presence of a hidden field of oncogene-mutant melanocytes within clinically normal skin, which may represent an earlier step in tumourigenesis. Objectives We aimed to determine whether BRAF V600E-mutant melanocytes were commonly present in non-lesional skin from adults at high risk of melanoma. Methods We examined BRAF V600E mutation in 97 histologically and clinically normal, non-lesional skin samples from a high-risk Australian melanoma cohort. The skin selected was adjacent to a naevus or a prior melanoma site, photodamaged skin proximal (∼5cm) from melanoma excision, and photoprotected skin distant from lesions, as well as a low-risk neonatal foreskin-derived melanoblasts. We used immunohistochemistry to locate BRAF V600E-mutant cells in histopathology sections, droplet digital PCR to determine the fractional abundance of BRAF V600E in whole skin, and single-cell RNA sequencing to confirm cells as melanocytes and detect their transcriptional programs. Results We identified BRAF V600E-mutant melanocytes in skin surrounding naevi and primary melanomas, even years after tumour excision. Fields of BRAF V600E-mutant melanocytes are commonly observed in the skin of patients at high risk for melanoma and are up to 20-fold more dense and 50% more frequent in tumour-adjacent skin. Field cells exhibit a gene expression profile characteristic of BRAF V600E-induced growth arrest, consistent with dormant yet genetically primed cells. Conclusions There is a reservoir of oncogene-harbouring melanocytes in normal skin. Our observations challenge the prevailing notion that melanocyte expression of BRAF V600E is inherently tumourigenic. The presence of such fields suggests that the scope of melanoma detection and prevention efforts might be extended beyond visible lesions, to encompass potentially precancerous fields of driver-mutant cells. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Melanocytic Nevus: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Melanocytic Nevus (condition). Clinician-written summaries and actionable practice insights. 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Retrospective design with cases selected only where dual multiplex IHC had already been ordered. Cases with nevoid melanoma or atypical nevus cells — the most diagnostically challenging scenarios — may not be fully represented.","practice_takeaway":"When using dual Melan-A/Ki67 multiplex IHC, look for stronger Melan-A red chromogen intensity in melanoma cells versus adjacent nevus cells — this visual cue can help delineate tumor extent and improve margin and Breslow depth assessment."}},{"doi":"10.1093/bjd/ljaf412","pmid":"41148046","title":"Subclinical Fields of\n BRAF V600E\n -Mutant Melanocytes Populate Human Skin and Are Enriched Around Melanoma and Naevi","journal_title":"British Journal of Dermatology","journal_issn":"0007-0963","published_at":"2025-10-28T00:00:00.000Z","url":"https://doi.org/10.1093/bjd/ljaf412","source_score":51,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2025-10-30","doi":"10.1093/bjd/ljaf412","days":"30","issn":"0007-0963","rank":"8","field":"Clinical Medicine","score":"51","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1093/bjd/ljaf412","title":"Subclinical Fields of BRAF V600E-Mutant Melanocytes Populate Human Skin and Are Enriched Around Melanoma and Naevi.","journal":"The British journal of dermatology","methods":"","results":"We identified BRAF V600E-mutant melanocytes in skin surrounding naevi and primary melanomas, even years after tumour excision. Fields of BRAF V600E-mutant melanocytes are commonly observed in the skin of patients at high risk for melanoma and are up to 20-fold more dense and 50% more frequent in tumour-adjacent skin. Field cells exhibit a gene expression profile characteristic of BRAF V600E-induced growth arrest, consistent with dormant yet genetically primed cells.","abstract":"$30","keywords":[],"pubmed_id":"41148046","conclusions":"","publication_date":"2025-10-28T00:00:00"},"crossref":{"DOI":"10.1093/bjd/ljaf412","URL":"https://doi.org/10.1093/bjd/ljaf412","ISSN":["0007-0963","1365-2133"],"link":[{"URL":"https://academic.oup.com/bjd/advance-article-pdf/doi/10.1093/bjd/ljaf412/65003382/ljaf412.pdf","content-type":"application/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https://academic.oup.com/bjd/advance-article-pdf/doi/10.1093/bjd/ljaf412/65003382/ljaf412.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Subclinical Fields of\n BRAF V600E\n -Mutant Melanocytes Populate Human Skin and Are Enriched Around Melanoma and Naevi"],"author":[{"given":"Katie J","family":"Lee","sequence":"first","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]},{"given":"Yung-Ching","family":"Kao","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]},{"given":"Amanda","family":"Jiang","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah Health Sciences Center , Salt Lake City, UT ,"},{"name":"Department of Oncological Sciences, University of Utah Health Sciences Center , Salt Lake City, UT ,"},{"name":"Department of Dermatology, University of Utah Health Sciences Center , Salt Lake City, UT ,"}]},{"given":"Anastasia","family":"Prokofyeva","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah Health Sciences Center , Salt Lake City, UT ,"},{"name":"Department of Oncological Sciences, University of Utah Health Sciences Center , Salt Lake City, UT ,"}]},{"given":"Lisa N","family":"Tom","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]},{"given":"Kasturee","family":"Jagirdar","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]},{"given":"Darren J","family":"Smit","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]},{"given":"Harald M","family":"Oey","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]},{"given":"Jean-Marie","family":"Tan","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]},{"given":"Stephen A","family":"Ainger","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]},{"given":"Nancy","family":"Huang","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]},{"given":"Zewen Kelvin","family":"Tuong","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]},{"given":"Stacey","family":"Andersen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland , Brisbane ,"}]},{"given":"Anne","family":"Senabouth","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research , Sydney ,"}]},{"given":"Joseph E","family":"Powell","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research , Sydney ,"},{"name":"UNSW Cellular Genomics Futures Institute , UNSW, Sydney ,"}]},{"given":"Duncan","family":"Lambie","sequence":"additional","affiliation":[{"name":"Sullivan Nicolaides Pathology , Brisbane ,"}]},{"given":"Helmut","family":"Schaider","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"},{"name":"Department of Dermatology, Princess Alexandra Hospital , Brisbane ,"}]},{"given":"H Peter","family":"Soyer","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"},{"name":"Department of Dermatology, Princess Alexandra Hospital , Brisbane ,"}]},{"given":"Richard A","family":"Sturm","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]},{"given":"Alana L","family":"Welm","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah Health Sciences Center , Salt Lake City, UT ,"},{"name":"Department of Oncological Sciences, University of Utah Health Sciences Center , Salt Lake City, UT ,"}]},{"given":"Douglas","family":"Grossman","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah Health Sciences Center , Salt Lake City, UT ,"},{"name":"Department of Dermatology, University of Utah Health Sciences Center , Salt Lake City, UT ,"}]},{"given":"Robert L","family":"Judson-Torres","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah Health Sciences Center , Salt Lake City, UT ,"},{"name":"Department of Oncological Sciences, University of Utah Health Sciences Center , Salt Lake City, UT ,"},{"name":"Department of Dermatology, University of Utah Health Sciences Center , Salt Lake City, UT ,"}]},{"given":"Mitchell S","family":"Stark","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Dermatology Research Centre , Brisbane ,"}]}],"issued":{"date-parts":[[2025,10,28]]},"member":"286","prefix":"10.1093","source":"Crossref","volume":null,"created":{"date-time":"2025-10-17T12:17:53Z","timestamp":1760703473000,"date-parts":[[2025,10,17]]},"indexed":{"date-time":"2025-10-28T15:20:34Z","timestamp":1761664834937,"date-parts":[[2025,10,28]]},"license":[{"URL":"https://creativecommons.org/licenses/by-nc/4.0/","start":{"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000,"date-parts":[[2025,10,28]]},"delay-in-days":0,"content-version":"am"}],"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://academic.oup.com/bjd/advance-article/doi/10.1093/bjd/ljaf412/8304794"}},"subtitle":[],"deposited":{"date-time":"2025-10-28T15:14:56Z","timestamp":1761664496000,"date-parts":[[2025,10,28]]},"issn-type":[{"type":"print","value":"0007-0963"},{"type":"electronic","value":"1365-2133"}],"published":{"date-parts":[[2025,10,28]]},"publisher":"Oxford University Press (OUP)","reference":null,"short-title":[],"article-number":"ljaf412","content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["British Journal of Dermatology"],"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2025,10,28]]},"references-count":0,"short-container-title":[],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1093/bjd/ljaf412","is_oa":false,"title":"Subclinical Fields of\n BRAF V600E\n -Mutant Melanocytes Populate Human Skin and Are Enriched Around Melanoma and Naevi","updated":"2025-10-30T03:32:29+00:00","published_date":"2025-10-17","best_oa_location":null}},"created_at":"2025-10-31T07:08:03.805Z","updated_at":"2025-11-29T07:06:31.192Z","tags":[{"paper_doi":"10.1093/bjd/ljaf412","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/bjd/ljaf412","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1093/bjd/ljaf412","tag_type":"condition","value":"Cutaneous Melanoma","value_numeric":null},{"paper_doi":"10.1093/bjd/ljaf412","tag_type":"condition","value":"Melanocytic Nevus","value_numeric":null},{"paper_doi":"10.1093/bjd/ljaf412","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1093/bjd/ljaf412","tag_type":"sample_size","value":"n=97","value_numeric":97},{"paper_doi":"10.1093/bjd/ljaf412","tag_type":"study_design","value":"Cross-Sectional","value_numeric":null},{"paper_doi":"10.1093/bjd/ljaf412","tag_type":"warning","value":"Relative differences are reported without raw counts or denominators in the abstract.","value_numeric":null},{"paper_doi":"10.1093/bjd/ljaf412","tag_type":"warning","value":"Study design classification is inferred from methods; no outcomes on melanoma incidence or progression are reported.","value_numeric":null},{"paper_doi":"10.1093/bjd/ljaf412","tag_type":"warning","value":"The abstract reports sample count (n=97) but not the number of patients or detailed sampling scheme.","value_numeric":null}],"summaries":{"what_studied":"In adults at high risk of melanoma, the investigators assessed 97 histologically and clinically normal skin samples from various sites (adjacent to a naevus or prior melanoma, photodamaged skin ~5 cm from melanoma excision, and photoprotected distant skin) using BRAF V600E immunohistochemistry, droplet digital PCR, and single-cell RNA sequencing; neonatal foreskin melanoblasts were included as low-risk comparators.","key_result":"BRAF V600E–mutant melanocytes were found in skin surrounding naevi and primary melanomas, including years after excision, and such fields were up to 20-fold more dense and 50% more frequent in tumour-adjacent skin.","limitations":"The abstract provides relative enrichment (up to 20-fold density, 50% frequency) without absolute counts or prevalence estimates, and does not specify the number of patients represented by the 97 samples.","practice_takeaway":"In melanoma-prone adults, normal-appearing skin—especially near melanomas or naevi—can harbor fields of BRAF V600E–mutant melanocytes with a growth-arrest signature; surveillance and prevention strategies may need to look beyond visible lesions."}},{"doi":"10.1016/j.jid.2024.04.031","pmid":"38897541","title":"RNA Therapy for Oncogenic NRAS-Driven Nevi Induces Apoptosis","journal_title":"Journal of Investigative Dermatology","journal_issn":"0022-202X","published_at":"2024-06-20T00:00:00.000Z","url":"https://doi.org/10.1016/j.jid.2024.04.031","source_score":154,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2024-06-27","doi":"10.1016/j.jid.2024.04.031","days":"30","issn":"0022-202X","rank":"5","field":"Clinical Medicine","score":"154","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1016/j.jid.2024.04.031","title":"RNA Therapy for Oncogenic NRAS-Driven Nevi Induces Apoptosis.","journal":"The Journal of investigative dermatology","methods":"","results":"","abstract":"RAS proteins regulate cell division, differentiation, and apoptosis through multiple downstream effector pathways. Oncogenic RAS variants are the commonest drivers in cancers; however, they also drive many benign lesions predisposing to malignancy, such as melanocytic nevi, thyroid nodules, and colonic polyps. Reversal of these benign lesions could reduce cancer incidence; however, the effects of oncogenic RAS have been notoriously difficult to target with downstream pathway inhibitors. In this study, we show effective suppression of oncogenic and currently undruggable NRAS","keywords":["Melanocyte","Nanoparticle","Oncogene","Skin","siRNA"],"pubmed_id":"38897541","conclusions":"","publication_date":"2024-06-20T00:00:00"},"crossref":{"DOI":"10.1016/j.jid.2024.04.031","URL":"https://doi.org/10.1016/j.jid.2024.04.031","ISSN":["0022-202X"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S0022202X24004494?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S0022202X24004494?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":"122-134.e11","type":"journal-article","issue":"1","score":1,"title":["RNA Therapy for Oncogenic NRAS-Driven Nevi Induces Apoptosis"],"author":[{"given":"Dale","family":"Bryant","sequence":"first","affiliation":[]},{"given":"Sara","family":"Barberan-Martin","sequence":"additional","affiliation":[]},{"given":"Ruhina","family":"Maeshima","sequence":"additional","affiliation":[]},{"given":"Ignacio","family":"del Valle Torres","sequence":"additional","affiliation":[]},{"given":"Mohammad","family":"Rabii","sequence":"additional","affiliation":[]},{"given":"William","family":"Baird","sequence":"additional","affiliation":[]},{"given":"Aimie","family":"Sauvadet","sequence":"additional","affiliation":[]},{"given":"Charalambos","family":"Demetriou","sequence":"additional","affiliation":[]},{"given":"Phoebe","family":"Jones","sequence":"additional","affiliation":[]},{"given":"Nicole","family":"Knöpfel","sequence":"additional","affiliation":[]},{"given":"Fanourios","family":"Michailidis","sequence":"additional","affiliation":[]},{"given":"Melissa","family":"Riachi","sequence":"additional","affiliation":[]},{"given":"Dorothy C.","family":"Bennett","sequence":"additional","affiliation":[]},{"given":"Davide","family":"Zecchin","sequence":"additional","affiliation":[]},{"given":"Alan","family":"Pittman","sequence":"additional","affiliation":[]},{"given":"Satyamaanasa","family":"Polubothu","sequence":"additional","affiliation":[]},{"given":"Stephen","family":"Hart","sequence":"additional","affiliation":[]},{"given":"Veronica A.","family":"Kinsler","sequence":"additional","affiliation":[]}],"funder":[{"id":[{"id":"10.13039/501100000272","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100000272","name":"NIHR","doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2025,1]]},"member":"78","prefix":"10.1016","source":"Crossref","volume":"145","created":{"date-time":"2024-06-17T09:08:25Z","timestamp":1718615305000,"date-parts":[[2024,6,17]]},"indexed":{"date-time":"2025-09-20T06:53:53Z","timestamp":1758351233702,"date-parts":[[2025,9,20]]},"license":[{"URL":"https://www.elsevier.com/tdm/userlicense/1.0/","start":{"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000,"date-parts":[[2025,1,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://www.elsevier.com/legal/tdmrep-license","start":{"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000,"date-parts":[[2025,1,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"http://creativecommons.org/licenses/by/4.0/","start":{"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000,"date-parts":[[2024,6,13]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":null,"language":"en","relation":{},"resource":{"primary":{"URL":"https://linkinghub.elsevier.com/retrieve/pii/S0022202X24004494"}},"subtitle":[],"assertion":[{"name":"publisher","label":"This article is maintained by","value":"Elsevier"},{"name":"articletitle","label":"Article Title","value":"RNA Therapy for Oncogenic NRAS-Driven Nevi Induces Apoptosis"},{"name":"journaltitle","label":"Journal Title","value":"Journal of Investigative Dermatology"},{"name":"articlelink","label":"CrossRef DOI link to publisher maintained version","value":"https://doi.org/10.1016/j.jid.2024.04.031"},{"name":"content_type","label":"Content Type","value":"article"},{"name":"copyright","label":"Copyright","value":"© 2024 The Authors. 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