Pigment Cell & Melanoma Research最新文献

{"title":"Dissecting the Spectrum of Rare BRAF Mutations in Melanoma: A Nation-Wide Study by the Italian Melanoma Intergroup (IMI).","authors":"Bruna Dalmasso, Maria Chiara Scaini, Laura Cendron, Monica Rodolfo, Ilaria Mattavelli, Elena Tamborini, Francesca Collina, Gerardo Ferrara, Gabriele Madonna, Carlo Cota, Elisa Melucci, Stefania Tommasi, Martina Ubaldi, Roberta Depenni, Andrea Carugno, Riccardo Marconcini, Laura Orgiano, Maurizio Lombardo, Simona Sola, Cristina Pellegrini, Francesca Castiglione, Matteo Gasparotto, Alireza Jorkesh, Stefania Pellegrini, Edoardo Raposio, Andrea Boutros, Enrica Teresa Tanda, Michele Guida, Pietro Quaglino, Giuseppe Palmieri, Daniela Massi, Paolo Antonio Ascierto, Francesco Spagnolo, Mario Mandalà, Chiara Menin, Paola Ghiorzo, Lorenza Pastorino","doi":"10.1111/pcmr.70087","DOIUrl":"10.1111/pcmr.70087","url":null,"abstract":"<p><p>Non-V600E/K BRAF mutations have been reported in melanoma, but data on their clinical relevance are conflicting. This study investigated the distribution, prognostic role, and functional impact of rare BRAF mutations in melanoma. We retrospectively assessed frequency, response to therapy and outcome of rare BRAF mutations compared to V600E/K in cases from 19 Italian Melanoma group (IMI) centers. 258/14,081 samples (1.8%) harbored rare BRAF mutations, 40% encompassing codon 600. Overall and progression-free survival (OS, PFS) following target therapy with BRAF/MEK inhibitors were comparable to V600E/K mutant melanoma (HR = 0.85 and 0.89, p > 0.1). Response to target therapy was lower, albeit not significantly, in rare BRAF mutant melanomas compared to V600E/K (48% vs. 66%, p > 0.05). OS, PFS, and objective response in cases treated with immunotherapy were unaffected by BRAF status. Molecular dynamics simulation assessing whether selected BRAF variants affected BRAF structure similarly to V600E showed variable degrees of destabilization towards constitutive protein activation, particularly for mutations encompassing codons 599-601. These results indicate that rare BRAF mutations can modify BRAF kinase activity including a subset of mutations outside but close to codon 600. Molecular approaches able to detect rare BRAF mutations could identify additional melanoma cases eligible for therapies with BRAF/MEK inhibitors.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"39 3","pages":"e70087"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721087","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":"Comparison of Disease Progression Between Amelanotic Melanoma and Melanotic Melanoma.","authors":"Barzilai Aviv, Barnea Hamama Noa, Levin Lotan, Baum Sharon","doi":"10.1111/pcmr.70083","DOIUrl":"https://doi.org/10.1111/pcmr.70083","url":null,"abstract":"<p><p>Amelanotic melanoma lacks melanin and is more challenging to diagnose than pigmented melanoma, often leading to delayed detection and worse outcomes. We conducted a retrospective cohort study of 322 patients (28 with amelanotic melanoma and 294 with melanotic melanoma) treated at Sheba Medical Center between 2017 and 2023. Clinical features, treatment modalities, and 1-year outcomes were analyzed. Tumor stage at diagnosis was the strongest predictor of remission, disease progression, and mortality in both groups. Pigmentation was associated with a higher likelihood of treatment modification (p = 0.02) and showed a borderline association with progression (p = 0.08). Subgroup analysis by stage revealed no significant outcome differences except for increased therapy change in stage 2 melanotic melanoma. The findings reinforce the importance of early detection, especially in amelanotic melanoma.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"39 3","pages":"e70083"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831368","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":"Rare Melanomas: An Area of Urgent Research and Clinical Need.","authors":"Keiran S M Smalley, Joan Levy","doi":"10.1111/pcmr.70088","DOIUrl":"https://doi.org/10.1111/pcmr.70088","url":null,"abstract":"","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"39 3","pages":"e70088"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809159","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":"Haplotype-Based Analysis of OCA2 Variants in Oculocutaneous Albinism","authors":"Meredith F. Gillis,&nbsp;Madeleine R. Ames,&nbsp;Linnea Lundh,&nbsp;Valer Gotea,&nbsp;Laura Elnitski,&nbsp;Frank Donovan,&nbsp;NISC Comparative Sequencing Program,&nbsp;Adebowale Adeyemo,&nbsp;Charles Rotimi,&nbsp;Brian Brooks,&nbsp;Wadih Zein,&nbsp;William Gahl,&nbsp;William S. Oetting,&nbsp;David R. Adams,&nbsp;Stacie K. Loftus","doi":"10.1111/pcmr.70085","DOIUrl":"10.1111/pcmr.70085","url":null,"abstract":"<p>OCA2, a melanosome transmembrane spanning protein, functions to regulate melanosomal pH, optimizing production of melanin pigment. <i>OCA2</i> is one of eight non-syndromic autosomal recessive oculocutaneous albinism (OCA) loci and is the second most common cause of OCA worldwide. Genome wide association studies (GWAS) have identified <i>OCA2</i> coding and regulatory variants linked to common skin and eye color pigment variation, skin cancer susceptibility, and retinal pigment epithelium tissue metrics. Within a cohort of 106 <i>OCA2</i> probands with two biallelic <i>OCA2</i> variants, a total of 74 distinct <i>OCA2</i> rare variants were identified (11 large structural, 17 small indel/frameshift, 12 splice site, and 34 missense coding variants). Phase-validated haplotypes, comprised of both <i>OCA2</i> common pigmentation trait GWAS alleles and rare variants, were obtained for 95/106 probands. In total, 41 distinct multi-allele <i>OCA2</i> haplotypes were identified with 27 haplotypes containing either rs1800404-A and/or rs12913832-G alleles, each of which is known to reduce correct isoform splicing or gene expression by ~20%. These results find that common GWAS alleles with known <i>OCA2</i> functional impact are present on haplotypes with variants of unknown significance in <i>OCA2</i> probands and highlight the need for haplotype-based analysis at the <i>OCA2</i> locus in addition to individual variant pathogenic assessment.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"39 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571521","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":"A Short Report on Melanocyte/Melanoma Culture, Senescence, and Reproducibility","authors":"Lionel Larue,&nbsp;ESPCR Working Group,&nbsp;Duarte C. Barral,&nbsp;Veronique Delmas,&nbsp;Sara Egea-Rodriguez,&nbsp;Daniel Aldea,&nbsp;Heather C. Etchevers,&nbsp;Marie-Dominique Galibert,&nbsp;Robert N. Kelsh,&nbsp;Luisa Lanfrancone,&nbsp;Michele Madigan,&nbsp;Pedro Moura-Alves,&nbsp;Richard M. White,&nbsp;Anja Bosserhoff","doi":"10.1111/pcmr.70084","DOIUrl":"10.1111/pcmr.70084","url":null,"abstract":"<p>At the 2025 ESPCR (<i>European Society for Pigment Cell Research</i>) meeting in Erlangen, a workshop on “Pigment Cell Models: Sensitivity, Innovation, and the Challenges of Cell Culture” brought together researchers to discuss technical, methodological, and reproducibility issues in culturing melanocytes, keratinocytes, fibroblasts, and melanoma cells. The discussion between experts in the field highlighted key and recurrent pitfalls affecting experimental outcomes, including low-density seeding, temperature fluctuations, over-passaging, and mycoplasma contamination, as well as sources of variability arising from media composition, batch effects, and environmental conditions. Importantly, the workshop distinguished between practices supported by evidence and consensus-based guidance derived from collective expert experience. Species- and donor-specific differences, especially between human, mouse, and zebrafish melanocyte models, were identified as additional major determinants of experimental variability. Emerging systems, including human and mouse pluripotent stem cell (PSC)-derived melanocytes, as well as avian and zebrafish melanoma lines, were discussed for their complementary mechanistic and translational value. Overall, the workshop concluded that transparent documentation, explicit reporting standards, and shared best practices are essential to improve reproducibility and further advance pigment cell research.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"39 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429448","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":"QUILPEN Provides Independent and Label-Free Single-Cell Quantification of Pigmentation Dynamics and Organelle Content","authors":"Rebecca G. Zitnay,&nbsp;Shukran Alizada,&nbsp;Tarek E. Moustafa,&nbsp;Devin Lange,&nbsp;Luke Schreiber,&nbsp;Alexander Lex,&nbsp;Robert L. Judson-Torres,&nbsp;Thomas A. Zangle,&nbsp;Rachel L. Belote","doi":"10.1111/pcmr.70080","DOIUrl":"10.1111/pcmr.70080","url":null,"abstract":"<p>The relationship between melanogenesis, pigmentation, and melanocyte behavior is complex. In melanocytes, pigmentation is often associated with differentiation, yet mature melanocytes vary in pigment content. In melanoma, pigmentation-linked transcriptional programs may have prognostic value, but visual assessments of tumor pigmentation have yielded inconsistent results. Progress linking pigmentation phenotypes to cell state has been limited by a lack of tools that can directly and dynamically quantify melanin content in live cells. Here we present QUantitative Imaging of Label-free Pigment-associated ENtities (QUILPEN), a label-free multimodal imaging technique that combines quantitative phase imaging (QPI), quadrant darkfield (QDF), and absorption imaging to independently capture light that has been transmitted, scattered, and absorbed. This nondestructive method enables live-cell imaging over multiple days without labels. We show absorption as a reliable readout of melanin content, which can be decoupled from melanosome content detected by QDF, which measures scattered light. Applying QUILPEN to melanoma cells before and during repigmentation, we find that melanin content is highly heterogeneous, and that this heterogeneity is reinstated upon repigmentation. Lineage tracking further reveals that melanin synthesis rates are heritable and can be transmitted both symmetrically and asymmetrically. QUILPEN enables real-time quantification of pigmentation dynamics and cell-level heterogeneity.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"39 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346978","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":"Independent BRAF Fusion Genes Cause Pigmented Nevi in Ring Chromosome 7 Syndrome","authors":"Akira Miyazaki,&nbsp;Takuya Takeichi,&nbsp;Mai Ota,&nbsp;Shoichiro Mori,&nbsp;Seiji Mizuno,&nbsp;Yoshinao Muro,&nbsp;Masashi Akiyama","doi":"10.1111/pcmr.70081","DOIUrl":"10.1111/pcmr.70081","url":null,"abstract":"","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"39 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147300463","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":"Rare Germline Variants in CDKN2A-Negative Children and Adolescents With Cutaneous Melanoma","authors":"Peter A. Johansson,&nbsp;Jane M. Palmer,&nbsp;Linh T. Bui-Raborn,&nbsp;Mai Xu,&nbsp;Kristine M. Jones,&nbsp;Herbert Higson,&nbsp;Jia Liu,&nbsp;Kelly M. Brooks,&nbsp;Antonia L. Pritchard,&nbsp;Nicholas K. Hayward,&nbsp;Kevin M. Brown","doi":"10.1111/pcmr.70079","DOIUrl":"10.1111/pcmr.70079","url":null,"abstract":"<p>Cutaneous melanoma is a complex disease influenced by both environmental and genetic factors. Inherited susceptibility plays a significant role, involving a combination of high-, intermediate- and low-penetrance genes. Melanoma in children and adolescents has been speculated to have a stronger genetic component due to the early onset. This study investigates germline variants in early-onset melanoma through exome sequencing of 154 patients in Australia diagnosed with cutaneous melanoma before the age of 20. Potentially pathogenic variants in shelterin complex genes were identified in 3% of the cases, consistent with a role for telomere dysregulation in early-onset melanoma. <i>MC1R</i> R-alleles, associated with red hair, fair skin and increased melanoma risk, were less frequent than in adult cases (0.46 vs. 0.64). Pathogenic germline variants in pigmentation genes linked to albinism were identified in 11 individuals (7%), including three truncating variants in <i>PMEL</i>, reinforcing the role of pigmentation pathways in cutaneous melanoma susceptibility. Two patients carried mutations in <i>MBD4</i>, suggesting it may contribute to early-onset disease. The high frequency of rare variants in high- or intermediate-risk genes highlights the importance of including such genes in genetic tests, as they may have implications for future risk in the adolescent patients and their at-risk relatives.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"39 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163238","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":"Recent Advances in Systemic Biomarkers for Immunotherapy in Advanced and Metastatic Melanoma","authors":"Chih-Yi Ho,&nbsp;Yu-Wen Cheng,&nbsp;Yang-Yi Chen","doi":"10.1111/pcmr.70046","DOIUrl":"10.1111/pcmr.70046","url":null,"abstract":"<p>Immune checkpoint inhibitor (ICI) therapy has been widely utilized across various cancer types, including melanoma. It has emerged as a first-line treatment option for metastatic melanoma. By targeting checkpoint proteins such as programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4), ICI therapy activates the immune system, enhancing its ability to combat cancer cells, leading to long-term efficacy and potential cures in some patients. However, ICI therapy is not universally effective. Resistance and adverse reactions of ICI therapy occur in some patients. The identification of systematic biomarkers from blood tests may offer a rapid and efficient means to assess patient responsiveness to ICI therapy, as well as the risk of developing immune-related adverse events (irAEs), to facilitate individualized patient selection. This article provides a comprehensive literature review of systemic biomarkers used in melanoma patients receiving ICI therapy. The insights provide clinical professionals and researchers with valuable information for the investigation and management of melanoma patients, leading toward personalized medical decisions.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"39 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130464","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":"Defining Important Aspects of Repigmentation in Vitiligo: Insights From Patients' Perspectives","authors":"Jolien Duponselle,&nbsp;Marlide R. Jukema,&nbsp;Nicoline van Buchem-Post,&nbsp;Liesbeth Delbaere,&nbsp;Amit Garg,&nbsp;Iltefat Hamzavi,&nbsp;Sandrine Herbelet,&nbsp;Julien Seneschal,&nbsp;Phyllis Spuls,&nbsp;Caroline B. Terwee,&nbsp;Sanne Uitentuis,&nbsp;Marloes Zuidgeest,&nbsp;Georg Pliszewski,&nbsp;Stephen Taylor,&nbsp;Sharon King,&nbsp;Maya Tulpule,&nbsp;Paul Monteiro,&nbsp;Nicolle Maquignon,&nbsp;Jean-Marie Meurant,&nbsp;Nathalie Ambersley,&nbsp;Alex Schneider,&nbsp;Emma Rush,&nbsp;Albert Wolkerstorfer,&nbsp;Reinhart Speeckaert,&nbsp;Nanja van Geel","doi":"10.1111/pcmr.70078","DOIUrl":"10.1111/pcmr.70078","url":null,"abstract":"<div>\u0000 \u0000 <p>Repigmentation is an essential outcome in vitiligo assessment, yet it remains broadly defined. While perspectives from vitiligo experts have been explored, gaining insights from patients is crucial for a more comprehensive understanding. Ultimately, this could contribute to the development and refinement of core outcome sets for vitiligo. This study aimed to determine aspects of repigmentation patients consider most important. Two surveys and one focus group were conducted, involving 34 patients/patient caregivers and 20 patient representatives. In the surveys, aspects were deemed important if ≥ 70% of participants rated them as such. The focus group used the nominal group technique to rank the five most important self-suggested aspects. The survey results indicate reduction of target lesion surface area, maintenance of repigmentation, and cessation of spread as important. The focus group identified additional aspects, including “time to repigment,” “location of lesions,” and “color match”. This study identified key aspects of repigmentation important to vitiligo patients. While survey results in general aligned with the core domain set for vitiligo clinical trials, the focus group highlighted additional factors. Incorporating these patient-centered priorities into future core outcome sets could enhance the clinical relevance of vitiligo research and ensure outcomes reflect patient perspectives.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"39 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122994","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}