{"title":"High-Risk Melanoma: Stage Before Operating","authors":"Stanislau Makaranka, Zon Oo, Jonathan Pollock","doi":"10.1111/pcmr.13213","DOIUrl":"10.1111/pcmr.13213","url":null,"abstract":"<div>\u0000 \u0000 <p>Current NICE guidelines state that in high-risk melanoma patients, imaging should not be offered before SLNB unless lymph node or distant metastases are suspected. Our experience has been that in patients with pT3b, pT4a and pT4b melanomas, the rate of management-changing findings on axial imaging prior to SLNB was high and that ‘stage before operating’ is a better approach. We now offer full axial imaging as staging to all high-risk melanoma patients prior to SLNB and advise other skin cancer MDTs to follow this approach.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764896","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}
{"title":"Mouse Tail-Skin Dissociation and Preparation of Live Single-Cell Suspension for Downstream Analysis of Melanocytes","authors":"Vipin Shankar Chelakkot, Kiara Thomas, Leen Hussein, Todd Romigh, Ying Ni, Joshua Arbesman","doi":"10.1111/pcmr.13216","DOIUrl":"10.1111/pcmr.13216","url":null,"abstract":"<div>\u0000 \u0000 <p>Isolating high-quality viable single cells from mouse tail skin, a well-established model for studying skin cells and melanoma pathogenesis, is challenging due to the presence of dense connective tissue and hair follicles. Single-cell RNA sequencing (scRNA-seq) is a powerful tool for studying skin cell heterogeneity. However, the lack of a robust protocol for the efficient generation of highly viable single-cell suspension from mouse tail skin has limited its application for studying melanocyte-interacting cells and characterizing the melanocyte niche. We developed a robust protocol for generating highly viable single-cell suspensions from mouse tail skin, facilitating single-cell transcriptomic profiling of keratinocytes, melanocytes, and fibroblasts. We demonstrate the successful isolation of melanocytes and other melanocyte-interacting cells using our protocol and a proof-of-concept scRNA-seq study for interrogating the melanocyte niche. Our protocol employs a two-stage enzyme dissociation step, followed by debris removal and subsequent live cell enrichment, to obtain a single-cell suspension with high cell viability. This straightforward protocol enables the isolation of viable single cells from mouse tail skin for downstream scRNA-seq studies. Further, this approach allows comprehensive analysis of the melanocyte niche and melanocyte-interacting cells, potentially aiding in identifying the melanoma cell of origin.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764905","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}
Alan Garcia-Elfring, Heather L. Roffey, Jaren M. Abergas, Jurgen Wuyts, Andrew P. Hendry, Athanasia C. Tzika, Rowan D. H. Barrett
{"title":"A Ball Python Colour Morph Implicates MC1R in Melanophore–Xanthophore Distribution and Pattern Formation","authors":"Alan Garcia-Elfring, Heather L. Roffey, Jaren M. Abergas, Jurgen Wuyts, Andrew P. Hendry, Athanasia C. Tzika, Rowan D. H. Barrett","doi":"10.1111/pcmr.13215","DOIUrl":"10.1111/pcmr.13215","url":null,"abstract":"<div>\u0000 \u0000 <p>Reptiles showcase an extensive array of skin colours and patterns, yet little is known about the genetics of reptile colouration. Here, we investigate the genetic basis of the Clown colour morph found in captive-bred ball pythons (<i>Python regius</i>) to study skin pigmentation and patterning in snakes. We obtained samples by crowdsourcing shed skin from commercial breeders and hobbyists. We applied a case–control design, whole-genome pool sequencing, variant annotation, histological analyses, and electron microscopy imaging. We identified a missense mutation in a transmembrane region of the <i>melanocortin-1 receptor</i> (<i>MC1R</i>) associated with the Clown phenotype. In classic avian and mammalian model species, MC1R is known for controlling the type and amount of melanin produced. In contrast, our results suggest that MC1R signalling might play a key role in pattern formation in ball pythons, affecting xanthophore–melanophore distribution. This work highlights the varied functions of MC1R across different vertebrate lineages and promotes a novel model system to study reptile colouration.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749525","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}
Barbara Anna Bokor, Aliasgari Abdolreza, Flóra Kaptás, Margit Pál, Zita Battyani, Márta Széll, Nikoletta Nagy
{"title":"Novel Variants in Medium and Low Penetrance Predisposing Genes in a Hungarian Malignant Melanoma Cohort With Increased Risk","authors":"Barbara Anna Bokor, Aliasgari Abdolreza, Flóra Kaptás, Margit Pál, Zita Battyani, Márta Széll, Nikoletta Nagy","doi":"10.1111/pcmr.13214","DOIUrl":"10.1111/pcmr.13214","url":null,"abstract":"<div>\u0000 \u0000 <p>Both germline and somatic variants contribute to the genetic background and pathogenesis of melanoma. Germline variants include the presence of rare pathogenic or likely pathogenic variants of high, medium, and low penetrance melanoma-predisposing genes. Rare variants of high penetrance melanoma-predisposing genes are associated with melanoma development, whereas the medium and low penetrance predisposing genes can significantly increase melanoma risk. In this study, we clarified the germline genetic background of a Hungarian melanoma cohort (<i>n</i> = 17). Using a gene panel of 30 melanoma-predisposing genes, germline genetic variants were identified in 10 of the 17 patients (58.82%). A novel, likely pathogenic, missense variant (p.Y143C) in a medium penetrance melanoma-predisposing gene, <i>melanocortin 1 receptor gene</i> (<i>MC1R</i>), and two novel, likely pathogenic nonsense variants in low penetrance genes, p.Q218Ter in caspase 8 (<i>CASP8</i>) and p.Q40Ter in the fat mass- and obesity-associated (<i>FTO</i>) gene were detected. This study highlights the importance of elucidating the germline genetic background of melanoma, which may improve prediction of individual risk and the risk of family members and to optimize preventive, screening, and therapeutic measures for each patient and melanoma-prone families.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749534","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}
{"title":"Exploring the Common Mutational Landscape in Cutaneous Melanoma and Pancreatic Cancer","authors":"Elisabetta Broseghini, Federico Venturi, Giulia Veronesi, Biagio Scotti, Marina Migliori, Desy Marini, Claudio Ricci, Riccardo Casadei, Manuela Ferracin, Emi Dika","doi":"10.1111/pcmr.13210","DOIUrl":"10.1111/pcmr.13210","url":null,"abstract":"<p>Cutaneous melanoma (CM) and pancreatic cancer are aggressive tumors whose incidences are rapidly increasing in the last years. This review aims to provide a complete and update description about mutational landscape in CM and pancreatic cancer, focusing on similarities of these two apparently so different tumors in terms of site, type of cell involved, and embryonic origin. The familial forms of CM and pancreatic cancers are often characterized by a common mutated gene, namely <i>CDKN2A</i>. In fact, a germline mutation in <i>CDKN2A</i> gene can be responsible for the development of the familial atypical multiple mole and melanoma syndrome (FAMMM), which is characterized by melanomas and pancreatic cancer development. Sporadic melanoma and pancreatic cancer showed different key-driven genes. The open-access resource cBioPortal has been explored to deepen and investigate the common mutational landscape of these two tumors. We investigated the common mutated genes found in both melanoma and pancreatic cancer with a frequency of at least 5% of tested patients and copy number alterations with a frequency of at least of 3%. Data showed that 18 mutated genes and 3 copy number alterations are present in both melanoma and pancreatic cancers types. Since we found two patients that developed both melanoma and pancreatic cancer, we compared mutation landscape between the two tumors and identified a pathogenic variant in <i>BRCA2</i> gene. This review gives valuable insights into the genetic underpinnings of melanoma and pancreatic cancer, urging the continued exploration and research of new genetic biomarkers able to identify patients and families at high risk of developing both cancers and to address to screening and to an effective clinical management of the patient.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749529","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}
Eleanor Johns, Yilun Ma, Pakavarin Louphrasitthiphol, Christopher Peralta, Miranda V. Hunter, Jeremy H. Raymond, Henrik Molina, Colin R. Goding, Richard M. White
{"title":"The Lipid Droplet Protein DHRS3 Is a Regulator of Melanoma Cell State","authors":"Eleanor Johns, Yilun Ma, Pakavarin Louphrasitthiphol, Christopher Peralta, Miranda V. Hunter, Jeremy H. Raymond, Henrik Molina, Colin R. Goding, Richard M. White","doi":"10.1111/pcmr.13208","DOIUrl":"10.1111/pcmr.13208","url":null,"abstract":"<div>\u0000 \u0000 <p>Lipid droplets are fat storage organelles composed of a protein envelope and lipid-rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role. To address this, we performed proteomic analysis of the lipid droplet envelope in melanoma. We found that lipid droplet proteins were differentially enriched in distinct melanoma states; from melanocytic to undifferentiated. DHRS3, which converts all-trans-retinal to all-trans-retinol, is upregulated in the MITF<sup>LO</sup>/undifferentiated/neural crest-like melanoma cell state and reduced in the MITF<sup>HI</sup>/melanocytic state. Increased DHRS3 expression is sufficient to drive MITF<sup>HI</sup>/melanocytic cells to a more undifferentiated/invasive state. These changes are due to retinoic acid-mediated regulation of melanocytic genes. Our data demonstrate that melanoma cell state can be regulated by expression of lipid droplet proteins which affect downstream retinoid signaling.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542417","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}
{"title":"UVA Irradiation Promotes Melanoma Cell Proliferation Mediated by OPN3 Independently of ROS Production","authors":"Yulei Zhang, Wen Zeng, Wei Zhang, Yu Wang, Shuqi Jin, Ting Liu, Huanhuan Luo, Hongguang Lu","doi":"10.1111/pcmr.13206","DOIUrl":"10.1111/pcmr.13206","url":null,"abstract":"<p>UVA radiation, a primary risk factor in melanoma progression, partly acts through the mediation of reactive oxygen species (ROS). The role of ROS in driving cutaneous melanoma toward an invasive phenotype and whether it occurs through opsins (OPNs), which are photosensitive G protein-coupled receptors, is not fully understood. This study focuses on the impact of UVA radiation on melanoma cell proliferation, with a special emphasis on OPN3. Investigating the biphasic response to various UVA doses (0.75–9 J/cm<sup>2</sup>) in A375 and MV3 cell lines, and using EdU and CCK-8 assays, we observed dose-dependent changes in cell proliferation. Interestingly, UVA irradiation at these doses of 0.75, 1.5 and 3 J/cm<sup>2</sup> did not significantly induce ROS production. Our study further delves into the role of OPN3, a photosensitive receptor, in melanoma progression. Following UVA exposure, an increase in OPN3 expression was observed in melanoma cells lines A375 and MV3, indicating its role as a UVA-sensitive sensor and its influence on cell proliferation. Additionally, UVA-induced calcium flux in two melanoma cells lines pointed to a calcium-dependent G protein-coupled pathway in melanoma proliferation, mediated by OPN3 and not reliant on ROS. This research sheds light on the mechanism of UVA-induced melanoma progression, underscoring OPN3 as a pivotal regulator and advancing our understanding of UVA's interaction with opsins in melanoma progression.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542418","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}
Juwon Moon, Ik Jun Moon, Hoyong Hyun, Jae Min Yoo, Seung Hyun Bang, Youngsup Song, Sung Eun Chang
{"title":"Bay 11-7082, an NF-κB Inhibitor, Prevents Post-Inflammatory Hyperpigmentation Through Inhibition of Inflammation and Melanogenesis","authors":"Juwon Moon, Ik Jun Moon, Hoyong Hyun, Jae Min Yoo, Seung Hyun Bang, Youngsup Song, Sung Eun Chang","doi":"10.1111/pcmr.13207","DOIUrl":"10.1111/pcmr.13207","url":null,"abstract":"<div>\u0000 \u0000 <p>Post-inflammatory hyperpigmentation (PIH) is a very common disorder of cutaneous hyperpigmentation, which poses a persistent management challenge in the fields of dermatology and esthetics. This study was designed to explore the anti-melanogenic and anti-inflammatory effects of Bay 11-7082, an NF-κB inhibitor, using small-molecule screening, to determine its potential application for PIH prevention. The molecular mechanisms were investigated in vitro and ex vivo in epidermis-humanized mice using melanin content, RT-PCR, and immunoblotting. Bay 11-7082 suppressed proinflammatory cytokines and ameliorated 2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis on day 15. The suppression of melanin synthesis by Bay 11-7082 was attributed to the reduction of MITF, which was induced by extracellular signal-regulated kinase activation. Bay 11-7082 reduced epidermal melanin accumulation in UVB-stimulated ex vivo human epidermis as well as in the ear and tail skin of K14-stem cell factor (SCF) transgenic mice. Topical administration of Bay 11-7082 improved PIH on day 35 in the post-DNFB dorsal skin of K14-SCF transgenic mice. In conclusion, Bay 11-7082 can be considered a promising candidate for the development of a preventive topical agent for PIH.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491757","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}
Zhonghui Hu, Lu Lu, Jindi Feng, Hongbin Song, Shiyu Zhang, Lu Yang, Yuehua Liu, Tao Wang
{"title":"Low-Dose Baricitinib Plus Narrow-Band Ultraviolet B for the Treatment of Progressive Non-Segmental Vitiligo: A Prospective, Controlled, Open-Label Study","authors":"Zhonghui Hu, Lu Lu, Jindi Feng, Hongbin Song, Shiyu Zhang, Lu Yang, Yuehua Liu, Tao Wang","doi":"10.1111/pcmr.13209","DOIUrl":"10.1111/pcmr.13209","url":null,"abstract":"<p>Vitiligo is a chronic autoimmune disease, and current treatments for vitiligo have limited efficacy. Janus kinase (JAK) inhibitors could offer new therapeutic options. To evaluate the efficacy and safety of baricitinib, an oral JAK1/2 inhibitor, combined with narrow-band ultraviolet B (NB-UVB) in vitiligo treatment. This prospective, controlled, open-label study included adults with progressive non-segmental vitiligo (NSV). Patients were assigned to combination therapy with baricitinib 2 mg daily and NB-UVB three times a week or NB-UVB alone three times a week (control). The primary endpoint was the proportion of patients achieving 50% or greater improvement from baseline in the total Vitiligo Area Scoring Index (T-VASI50) at week 16. Of the 33 patients (mean age, 34.1 years; 27.3% women) who completed the study, 12 of 17 (70.6%) patients in the combination group and 2 of 16 (12.5%) in the control group had a T-VASI50 response at week 16 (relative risk [RR] = 5.6; 95% CI = 1.5–21.4; <i>p</i> = 0.001). Adverse events were minor, including erythema, mild blister after phototherapy and acne. Combination therapy with low-dose baricitinib and NB-UVB was effective and well tolerated in adults with progressive NSV.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491758","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}
{"title":"25th Annual meeting of the European Society for Pigment Cell Research, Marseille, France","authors":"","doi":"10.1111/pcmr.13192","DOIUrl":"https://doi.org/10.1111/pcmr.13192","url":null,"abstract":"","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 5","pages":"713-740"},"PeriodicalIF":3.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435521","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}