Pigment Cell & Melanoma Research最新文献

Association of Pretreatment Tumour Microenvironment and Treatment Outcome in Patients With Locally Advanced Melanoma Treated With Isolated Limb Perfusion 局部晚期黑色素瘤患者分离肢体灌注治疗前肿瘤微环境与治疗结果的关系

IF 3.9 3区医学

Pigment Cell & Melanoma Research Pub Date : 2025-07-23 DOI: 10.1111/pcmr.70040

Sanni K. A. Tulokas, Susanna Juteau, Siru P. Mäkelä, Katja E. Välimäki, Teijo Pellinen, Micaela M. Hernberg

{"title":"Association of Pretreatment Tumour Microenvironment and Treatment Outcome in Patients With Locally Advanced Melanoma Treated With Isolated Limb Perfusion","authors":"Sanni K. A. Tulokas, Susanna Juteau, Siru P. Mäkelä, Katja E. Välimäki, Teijo Pellinen, Micaela M. Hernberg","doi":"10.1111/pcmr.70040","DOIUrl":"https://doi.org/10.1111/pcmr.70040","url":null,"abstract":"<p>As effective melanoma treatments have become available, utilizing isolated limb perfusion (ILP) to treat unresectable melanoma limited to the limb has decreased. However, some patients still receive long-term benefits from ILP. We aimed to identify features of the pretreatment tumor microenvironment (TME) to identify patients who may benefit from ILP. Pretreatment metastatic melanoma samples from 22 patients treated at Helsinki University Hospital with ILP from 2008 to 2018 were analyzed with multiplex immunohistochemistry (mIHC) and digital image analysis. Antibody panels evaluated the proportions of immune cells in the intratumoral and extratumoral compartments. We examined whether treatment response and median progression-free survival (PFS) after ILP correlated to findings in the TME. A statistically significant positive correlation was found between PFS and lower immune cell infiltrations in the intratumoral compartment (CD3+, CD4+, and CD11c+ cells), and increased numbers of immune cells in the extratumoral compartment were associated with longer PFS (CD3+, CD4+, CD8+, all expressing PD-1). Furthermore, the distribution of some immune cell subsets correlated with complete treatment response (PD-1/PD-L1-positive CD4+ and PD-1-positive CD8+ cells). Our results suggest that patients may have a better ILP outcome if the metastases exhibit a lower distribution of specific immune cell subtypes intratumorally and a higher extratumoral distribution of some immune cell subtypes.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pigmentation and Retinal Pigment Epithelium Thickness: A Study of the Phenotypic and Genotypic Relationships Between Ocular and Extraocular Pigmented Tissues 色素沉着和视网膜色素上皮厚度：眼和眼外色素组织表型和基因型关系的研究

IF 3.9 3区医学

Pigment Cell & Melanoma Research Pub Date : 2025-07-12 DOI: 10.1111/pcmr.70038

Thomas H Julian, Tomas Fitzgerald, UK Biobank Eye and Vision Consortium, Ewan Birney, Panagiotis I. Sergouniotis

{"title":"Pigmentation and Retinal Pigment Epithelium Thickness: A Study of the Phenotypic and Genotypic Relationships Between Ocular and Extraocular Pigmented Tissues","authors":"Thomas H Julian, Tomas Fitzgerald, UK Biobank Eye and Vision Consortium, Ewan Birney, Panagiotis I. Sergouniotis","doi":"10.1111/pcmr.70038","DOIUrl":"https://doi.org/10.1111/pcmr.70038","url":null,"abstract":"<p>The retinal pigment epithelium (RPE) is a specialised monolayer of pigmented epithelial cells in the outer retina. The extent to which RPE pigmentation is related to that of other tissues remains unclear. We utilised RPE thickness measured using optical coherence tomography (OCT) imaging as an indicator of RPE melanin content. UK Biobank data was used to assess the relationships between RPE thickness and fundus pigmentation, hair colour, skin colour and ability to tan. We performed a genome-wide association study (GWAS) to identify genetic loci associated with RPE thickness. We explored the genetic correlation between RPE thickness and pigmentation-related traits. We found that RPE thickness was not phenotypically or globally genetically correlated with hair colour, skin colour or ability to tan. Whilst RPE thickness was phenotypically correlated with fundus pigmentation, there was not significant global genetic correlation. Despite this, variants in key pigmentation loci including <i>TYR</i> and <i>OCA2</i>-<i>HERC2</i> were significant in our GWAS of RPE thickness. We identified four genetic regions in which RPE thickness is locally genetically correlated with other pigmentation-related traits, all of which contain protein-coding genes that are central to melanogenesis and melanosome transport. Our study highlights shared and divergent features between RPE thickness and other pigmented traits.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Proposed Categorization of Vitiligo Lesions on the Hands 建议对手部白癜风病变进行分类

IF 3.9 3区医学

Pigment Cell & Melanoma Research Pub Date : 2025-07-10 DOI: 10.1111/pcmr.70039

Kazunori Yokoi, Yosuke Ishitsuka, Kanae Kusao, Jing Wang, Haruna Kawashima, Narumi Jikihara, Seitaro Nakagawa, Eiji Kiyohara, Noriko Arase, Manabu Fujimoto, Atsushi Tanemura

{"title":"The Proposed Categorization of Vitiligo Lesions on the Hands","authors":"Kazunori Yokoi, Yosuke Ishitsuka, Kanae Kusao, Jing Wang, Haruna Kawashima, Narumi Jikihara, Seitaro Nakagawa, Eiji Kiyohara, Noriko Arase, Manabu Fujimoto, Atsushi Tanemura","doi":"10.1111/pcmr.70039","DOIUrl":"https://doi.org/10.1111/pcmr.70039","url":null,"abstract":"<p>Vitiligo is a common depigmentation disorder characterized by patchy white macules. It has been reported that vitiligo lesions, particularly in exposed areas, such as the face and hands, cause severe psychological distress. Although the classification and outcome of facial vitiligo have been proposed, clinical analyses featuring hand vitiligo are very limited, irrespective of its severe psychological impact. In this study, we investigated hand lesions in nonsegmental vitiligo patients and found that the distribution of hand vitiligo was symmetric, whereas the dominant hand was more frequently affected. Moreover, our clustering analysis newly classified hand vitiligo lesions into four distinct subtypes (<i>n</i> = 140): focal/scattered (46.4%), distal digit (31.4%), universal (12.9%), and proximal digit (9.2%) and their clinical characteristics. The focal/scattered type is the most common subtype and exhibits a distinctive prevalence in pediatric cases. The distal digit type was suggested to be associated with smoking or the Koebner phenomenon. The universal type is a distinct subtype, with onset in older age and a poor response to treatment. The proximal digit type is the rarest subtype, with onset at a young age. In conclusion, these findings deepen our understanding of the heterogeneity of hand vitiligo and support the development of personalized treatment strategies.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PRMT6 Inhibits Malignant Progression of Melanoma by Antagonizing Trimethylation of Histone H3K4 to Downregulate ALDH1A1 Levels PRMT6通过拮抗组蛋白H3K4三甲基化下调ALDH1A1水平抑制黑色素瘤恶性进展

IF 3.9 3区医学

Pigment Cell & Melanoma Research Pub Date : 2025-07-09 DOI: 10.1111/pcmr.70034

Man Cai, Liangyu Wang, Miao Sun, Meixi Liu, Yingchun Liu

{"title":"PRMT6 Inhibits Malignant Progression of Melanoma by Antagonizing Trimethylation of Histone H3K4 to Downregulate ALDH1A1 Levels","authors":"Man Cai, Liangyu Wang, Miao Sun, Meixi Liu, Yingchun Liu","doi":"10.1111/pcmr.70034","DOIUrl":"https://doi.org/10.1111/pcmr.70034","url":null,"abstract":"<div>\u0000 \u0000 <p>Protein arginine methyltransferase 6 (PRMT6), a member of the PRMT family capable of self-arginine methylation, is down-regulated in melanoma, but the specific mechanism is still unclear. Our work demonstrated that PRMT6 overexpression significantly inhibited the ability of melanoma cells to proliferate, tumorigenicity, migration, and invasion, whereas PRMT6 knockdown rescued these malignant behaviors of melanoma cells. Mechanistically, we identified aldehyde dehydrogenase 1A1 (ALDH1A1) as a critical downstream target of PRMT6. PRMT6 knockdown up-regulated ALDH1A1 expression, exacerbating melanoma aggressiveness in vitro. Further investigations revealed that PRMT6 modulates ALDH1A1 expression by catalyzing asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a) and antagonizing the enrichment of histone H3 lysine 4 trimethylation (H3K4me3) at the ALDH1A1 promoter. In addition, dual-luciferase experiments showed that the transcription factor KLF4 may bind to the −1800 ~ +45 sequence of PRMT6, thereby negatively regulating PRMT6 expression in melanoma. Our findings underscore the tumor-suppressive role of PRMT6 in melanoma pathogenesis, highlighting its potential as a novel therapeutic target, particularly for metastatic melanoma.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

YAP Upregulation Contributes to Acquired Resistance to BET Inhibitors in Uveal Melanoma YAP上调有助于葡萄膜黑色素瘤对BET抑制剂的获得性耐药性

IF 3.9 3区医学

Pigment Cell & Melanoma Research Pub Date : 2025-07-07 DOI: 10.1111/pcmr.70036

Yan-ling Zhou, Xiao-lian Liu, Si-Si Huang, Gui-ming Zhang, Xuan-yu Jin, Liang Chen, Le Yu, Yi-lei Li

{"title":"YAP Upregulation Contributes to Acquired Resistance to BET Inhibitors in Uveal Melanoma","authors":"Yan-ling Zhou, Xiao-lian Liu, Si-Si Huang, Gui-ming Zhang, Xuan-yu Jin, Liang Chen, Le Yu, Yi-lei Li","doi":"10.1111/pcmr.70036","DOIUrl":"https://doi.org/10.1111/pcmr.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>BET inhibitors have the potential to treat malignant tumors via the epigenetic modification mechanism. Although BET inhibitors show promise as anticancer agents for uveal melanoma (UM), the emergence of acquired resistance significantly limits their clinical efficacy. We developed isogenic OTX015-resistant UM cell models (OMM2.3R and OMM2.5R) via exposure to escalating OTX015 concentrations (0.04–0.5 μM over 6 months). These resistant cells demonstrated reduced sensitivity to OTX015-induced cytotoxicity. Moreover, the migratory ability of resistant cells was less affected by OTX015 compared to parental cells. Transcriptome analysis revealed an upregulation of YAP-activated genes in resistant cells. Notably, OTX015-resistant cells retained sensitivity to YAP inhibition via shRNA or pharmacological inhibitors. This study establishes YAP activation as a novel compensatory mechanism driving BET inhibitor resistance in UM. These findings position YAP inhibition as a potential therapeutic target to overcome BET inhibitor resistance, with clinical translational potential for resistant UM patients.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epidermotropic Metastatic Melanoma Presenting as Eruptive Primary Melanomas 表皮性转移性黑色素瘤表现为发疹性原发性黑色素瘤

IF 3.9 3区医学

Pigment Cell & Melanoma Research Pub Date : 2025-07-04 DOI: 10.1111/pcmr.70037

Jennifer Strong, Mitchell J. Winkie, Patrick Hallaert, Scott B. Whitecar, Elaine S. Keung, Daniel Neelon, Karen G. Zeman, Michele M. Gage, William C. Schaffenburg, Meagan M. Simpson, Isaac Brownell

{"title":"Epidermotropic Metastatic Melanoma Presenting as Eruptive Primary Melanomas","authors":"Jennifer Strong, Mitchell J. Winkie, Patrick Hallaert, Scott B. Whitecar, Elaine S. Keung, Daniel Neelon, Karen G. Zeman, Michele M. Gage, William C. Schaffenburg, Meagan M. Simpson, Isaac Brownell","doi":"10.1111/pcmr.70037","DOIUrl":"https://doi.org/10.1111/pcmr.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>We report on the use of molecular profiling to diagnose epidermotropic metastatic melanoma (EMM) in a patient who presented with eruptive primary melanomas. On histopathology, the patient's metastatic lesions resembled superficial spreading melanomas and were indistinguishable from independent primary melanomas. The patient's presumed primary melanoma was a stage IIIB nodular melanoma. Despite treatment with adjuvant nivolumab, the patient continued to form new superficial spreading melanomas. Due to suspicion for EMM, commercial panel sequencing was performed on tissue from four tumors. Comparison of reported somatic variants revealed a mutational profile that was conserved across all four lesions, establishing a diagnosis of stage IV EMM. Considering the progressive disease on immunotherapy, treatment was transitioned to encorafenib plus binimetinib, resulting in regression of existing lesions and cessation of new skin lesion formation. Aside from micrometastatic sentinel lymph node deposits from the presumed primary melanoma, the patient had no evidence of non-cutaneous metastases. EMM should be considered as a diagnosis for multiple superficial spreading melanomas arising synchronously or in rapid succession. As EMM and primary melanomas are often histopathologically indistinguishable, next generation sequencing is a valuable tool to confirm clonality and provide a definitive diagnosis.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prospective Isolation According to Melanin Pigment Content of Melanoma Cells With Heterogeneous Potentials for Disease Propagation 具有异质繁殖潜能的黑色素瘤细胞黑色素含量的前瞻性分离

IF 3.9 3区医学

Pigment Cell & Melanoma Research Pub Date : 2025-06-30 DOI: 10.1111/pcmr.70011

Clare Fedele, Gamze Kuser-Abali, Ralph Rossi, Peinan Zhao, Jason Li, Malaka Ameratunga, Pacman Szeto, YouFang Zhang, Miles Andrews, Mark Shackleton

{"title":"Prospective Isolation According to Melanin Pigment Content of Melanoma Cells With Heterogeneous Potentials for Disease Propagation","authors":"Clare Fedele, Gamze Kuser-Abali, Ralph Rossi, Peinan Zhao, Jason Li, Malaka Ameratunga, Pacman Szeto, YouFang Zhang, Miles Andrews, Mark Shackleton","doi":"10.1111/pcmr.70011","DOIUrl":"https://doi.org/10.1111/pcmr.70011","url":null,"abstract":"<p>Intra-tumoral heterogeneity poses a major challenge to treating and managing cancer patients. A characteristic feature of melanoma is its composition of cancer cells with typically heterogeneous content of melanin pigment, the production of which is a hallmark of normal melanocytic differentiation but of poorly understood consequence in melanoma cells, as prospective assessment of pigment heterogeneity in melanoma cells has been experimentally challenging. Here, we describe a novel flow cytometric method for high purity separation of viable melanoma cells based on their melanin content, exploiting the light scattering properties of melanin. By fluorescence-activated cell sorting, we show that cells with low-pigment content (LPCs) in melanoma cell lines and patient tumors are usually far more abundant than high-pigment cells (HPCs) and have substantially increased potentials for colony formation in vitro and tumor formation in vivo. In RNAseq analysis, HPCs showed P53 activation and perturbed cell cycling, whereas LPCs displayed upregulation of MYC-associated transcription and activated ribosome biogenesis. In proof-of-concept studies, the latter was targeted by topoisomerase 2 beta targeting with CX-5461, which induced senescent HPC phenotypes and irreversible loss of clonogenic activity. These data indicate an ‘inverted pyramid’ hierarchical model of melanoma cell propagation wherein abundant LPCs frequently renew their own malignant potential to propagate disease but also infrequently generate HPCs that spontaneously lose this ability in a manner that might be exploited as an anti-melanoma strategy.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunotherapy Rechallenge Is Effective for Most Patients With Late Progression After Initial Ipilimumab + Nivolumab Response 免疫疗法Rechallenge对大多数Ipilimumab + Nivolumab初始应答后晚期进展的患者有效

IF 3.9 3区医学

Pigment Cell & Melanoma Research Pub Date : 2025-06-18 DOI: 10.1111/pcmr.70023

Ethan Trim, Anita Giobbie-Hurder, Tamara A. Sussman, David Liu, Megan Insco, Rizwan Haq, F. Stephen Hodi, Patrick A. Ott, Elizabeth I. Buchbinder

{"title":"Immunotherapy Rechallenge Is Effective for Most Patients With Late Progression After Initial Ipilimumab + Nivolumab Response","authors":"Ethan Trim, Anita Giobbie-Hurder, Tamara A. Sussman, David Liu, Megan Insco, Rizwan Haq, F. Stephen Hodi, Patrick A. Ott, Elizabeth I. Buchbinder","doi":"10.1111/pcmr.70023","DOIUrl":"https://doi.org/10.1111/pcmr.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>Clinical benefit achieved with ipilimumab + nivolumab combination therapy is typically long lasting. However, late progression, after therapy completion, does occur in a subset of patients. At the time of late progression, immunotherapy options include anti-PD-1 monotherapy, anti-PD-1/LAG-3, repeat anti-PD-1/CTLA-4 therapy, or TIL therapy, but the efficacy of these approaches is unknown. To investigate, we evaluated 230 patients with advanced melanoma who received treatment with ipilimumab + nivolumab at Dana-Farber Cancer Institute between 2015 and 2022 as first-line treatment. Of these, 111 had an initial response of stable disease (SD) or better for 6 months or longer. Of the 111 deriving clinical benefit, 19 had late progression, 14 while off therapy. Ten of the 14 patients who had late progression off therapy were rechallenged with immune checkpoint inhibition (ICB), either as monotherapy or in combination. Eight out of those 10 patients had clinical benefit of SD or better upon ICB rechallenge. The two who did not benefit from rechallenge had mucosal melanoma (3 patients had mucosal, 7 had cutaneous). The data indicate that clinical benefit upon rechallenge with ICB can be achieved in the majority of patients, specifically those with the cutaneous subtype, although responses are mostly SD and are relatively short lived.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disruption of mc1r Disturbs Skin Pigmentation in Xenopus tropicalis mc1r的破坏扰乱了热带非洲爪蟾的皮肤色素沉着

IF 3.9 3区医学

Pigment Cell & Melanoma Research Pub Date : 2025-06-16 DOI: 10.1111/pcmr.70033

Lanxin Li, Jixuan Huang, Yonglong Chen, Rensen Ran

引用次数: 0

SASH1 Mutations and Hereditary Disorders of Pigmentation: Review of Literature SASH1突变与色素沉着遗传性疾病：文献综述

IF 3.9 3区医学

Pigment Cell & Melanoma Research Pub Date : 2025-06-13 DOI: 10.1111/pcmr.70032

Anuradha Bishnoi, Aarushi Arunima, Keshavamurthy Vinay, Muthu Sendhil Kumaran, Davinder Parsad

{"title":"SASH1 Mutations and Hereditary Disorders of Pigmentation: Review of Literature","authors":"Anuradha Bishnoi, Aarushi Arunima, Keshavamurthy Vinay, Muthu Sendhil Kumaran, Davinder Parsad","doi":"10.1111/pcmr.70032","DOIUrl":"https://doi.org/10.1111/pcmr.70032","url":null,"abstract":"<p>Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis characterized by asymptomatic hyper- and hypopigmented macules appearing in infancy and persisting for life. Although mutations in ABCB6 account for many DUH cases, recently, the SAM and SH3 domain-containing 1 (SASH1) gene has emerged as a key player in DUH. Additionally, SASH1 mutations have been associated with the pure-lentiginous phenotype of familial pigmentation. In this review of literature, we found 22 different SASH1 mutations, most inherited in an autosomal dominant manner. These variants cause distinct phenotypes, including DUH, lentiginosis, and rarely, an autosomal recessive syndromic form with alopecia, palmoplantar keratoderma, and increased risk of malignancies. Functional studies have revealed that SASH1 acts as both a tumor suppressor and a pro-melanogenic factor. It modulates key pathways such as p53–POMC–α-MSH–MC1R–MITF and Gαs-SASH1–IQGAP1–E-cadherin pathways, affecting melanosome production, transport, and melanocyte migration. This unique dual role of SASH1 highlights its importance in melanocyte homeostasis and UV-induced pigmentation. Understanding the role of SASH1 in regulating pigmentation can help foster novel therapeutic approaches for these genodermatoses and related pigmentary anomalies, ultimately improving patient care and outcomes.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0