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The study measured mutation load in mouse (n=23) and human (n=37) epidermis and found UV-related mutations accumulate in a dose-dependent manner and correlate with keratinocyte cancer burden. Epidermal ablation, followed by spontaneous healing, markedly reduced mutation load and lowered incident lesions in a UV-induced basal cell carcinoma model.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/epidermal-mutation-accumulation-in-photodamaged-skin-is-associated-with-skin-cancer-burden-and-can-be-targeted-through-ablative-therapy/376757/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/epidermal-mutation-accumulation-in-photodamaged-skin-is-associated-with-skin-cancer-burden-and-can-be-targeted-through-ablative-therapy/376757.png","ImageObject",300,407,{"name":92,"@type":93},"Asher","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",15,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main environmental driver of keratinocyte skin cancer in the document?","Question",{"text":113,"@type":114},"Solar ultraviolet (UV) irradiation is described as the main environmental factor driving keratinocyte skin cancer formation.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How did the study assess the relationship between UV exposure and epidermal mutation load?",{"text":118,"@type":114},"It examined mutation load in murine (n=23) and human (n=37) epidermal samples and evaluated how epidermal mutations accumulated in a UV dose-dependent manner.",{"name":120,"@type":111,"acceptedAnswer":121},"What intervention reduced epidermal mutation load and how did it affect cancer outcomes?",{"text":122,"@type":114},"Epidermal ablation (mechanical or laser-induced) followed by spontaneous healing reduced mutation load markedly in both mouse and human trials, and in a UV-induced basal cell carcinoma model reduced incident lesions by over 80%.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},376757,1790293818,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},687197207639,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","CANCER  \nEpidermal mutation accumulation in photodamaged skin is associated with skin cancer burden and can be targeted through ablative therapy  \nHo Yi Wong1,2, Ruby C. Lee1,2,3, Sharene Chong1,2,3, Stuti Kapadia1,2, Michael Freeman3, Valentine Murigneux4, Susan Brown1,3, H. Peter Soyer2,3, Edwige Roy1,2†,  \nKiarash Khosrotehrani1,2,3*†  \nThe main carcinogen for keratinocyte skin cancers (KCs) such as basal and squamous cell carcinomas is ultraviolet (UV) radiation. There is growing evidence that accumulation of mutations and clonal expansion play a key role in KC development. The relationship between UV exposure, epidermal mutation load, and KCs remains unclear. Here, we examined the mutation load in both murine (n = 23) and human (n = 37) epidermal samples. Epidermal mutations accumulated in a UV dose–dependent manner, and this mutation load correlated with the KC burden. Epidermal ablation (either mechanical or laser induced), followed by spontaneous healing from underlying epithelial adnexae reduced the mutation load markedly in both mouse (n = 8) and human (n = 6) clinical trials. In a model of UV-induced basal cell carcinoma, epidermal ablation reduced incident lesions by >80%(n = 5). Overall, our findings suggest that mutation burden is strongly associated with KC burden and represents a target to prevent subsequent KCs.  \nCopyright © 2023 The Authors, some  \nrights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC) .  \nINTRODUCTION  \nKeratinocyte skin cancers (KCs) are the most common malignancy (1) . The two major types ofKCs, basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), originate from the epidermis and represent a major global health burden. In Australia alone, there are more than a million interventions annually for KCs through mostly surgical excision (2, 3) . The main environmental factor driving KC formation is solar ultraviolet (UV) irradiation. This is also reflected in several key patient-associated risk factors ofKCs such as skin type and age. Red hair, inability to tan, and propensity to sunburn are key elements determining the risk of skin cancer at the individual level (4) . Similarly, advancing age is another important factor associated with KC formation (5) . The cumulative effect of sun damage is classically thought to result in field cancerization, where the entire area of the skin exposed to the sun is susceptible to cancer development. The high burden of the disease is due to multiplicity of new KCs—more than 50 to 80% of patients  \nwith a history of KCs will develop subsequent KCs (2, 5) .  \nUV exposure is thought to contribute to carcinogenesis through a variety of mechanisms. It induces mutations directly (6, 7), allows the expansion of clones through a proliferative stimulus (8), and acts as an immunosuppressant (9) . Recently, multiple studies reported that normal skin exposed to the sun could harbor mutations commonly found in KCs ( 10–13) . This suggests that carcinogenesis might be a more complex and intricate process, and simple disruption of genes that are commonly considered as cancer causing may not be enough to drive KCs. This was replicated in murine studies  \n1Dermatology Research Centre, Experimental Dermatology Group, Frazer Institute, The University of Queensland, Brisbane, Australia. 2Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia. 3Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia. 4QCIF Facility for Advanced Bioinformatics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.  \n*Corresponding author. Email: [k.khosrotehrani@uq.edu.au](k.khosrotehrani@uq.edu.au)[ ](k.khosrotehrani@uq.edu.au)†These authors contributed equally to this work.  \nwhere single oncogenic events were not enough to driv","cbCaimQHJ5oADHZH","https://ap.wps.com/l/cbCaimQHJ5oADHZH","pdf",1547783,13,"English","# Introduction\n## UV exposure and keratinocyte cancer risk\n## Mutation accumulation and field cancerization\n# Results\n## Chronic suberythemal UV exposure promotes mutation accumulation over time\n# Conclusion","[{\"question\":\"What is the main environmental driver of keratinocyte skin cancer in the document?\",\"answer\":\"Solar ultraviolet (UV) irradiation is described as the main environmental factor driving keratinocyte skin cancer formation.\"},{\"question\":\"How did the study assess the relationship between UV exposure and epidermal mutation load?\",\"answer\":\"It examined mutation load in murine (n=23) and human (n=37) epidermal samples and evaluated how epidermal mutations accumulated in a UV dose-dependent manner.\"},{\"question\":\"What intervention reduced epidermal mutation load and how did it affect cancer outcomes?\",\"answer\":\"Epidermal ablation (mechanical or laser-induced) followed by spontaneous healing reduced mutation load markedly in both mouse and human trials, and in a UV-induced basal cell carcinoma model reduced incident lesions by over 80%.\"}]","Epidermal mutation accumulation in photodamaged skin is associated with skin cancer burden and can be targeted through ablative therapy | PDF",1790221029,33]