Pigment Cell & Melanoma Research最新文献

The transcription factor SOX10 plays an important role in promoting determination and differentiation of melanocytes, and mutations affecting SOX10 expression or function often result in dramatic pigment phenotypes. In domestic rock pigeon, homozygosity for either of two regulatory mutations upstream of Sox10 known as recessive red causes birds to display bright red pheomelanic plumage instead of wild-type blue/black eumelanic plumage. In this study, we identify a common set of differentially expressed melanogenic genes in feathers from recessive red birds homozygous for either mutant allele, most notably a downregulation of Tyrp1, Slc24a5, Pmel, Mlana, and Hpgds and upregulation of Slc7a11. Collectively, these changes may promote pheomelanin synthesis and inhibit eumelanin synthesis. We also identify other altered pathways including genes involved in galactolipid synthesis and stem cell biology. We further examined the chromatin occupancy of SOX10 in pigeon melanocytes by ChIPseq to identify the subset of differentially expressed genes that are most likely to be direct targets of SOX10 function, and uncover evidence that SOX10 promotes its own expression by binding to the mcs7 melanocyte enhancer. Together, these data provide a more comprehensive picture of the role that SOX10 plays in melanocyte biology.

This article highlights the most recent updates in vitiligo that were presented in the sixth Vitiligo International Symposium, which was held in Cairo, Egypt from 13 to 15 December 2024. During this conference, worldwide vitiligo experts shared their experience in the different aspects of vitiligo, starting with vitiligo pathogenesis and all the basic science behind vitiligo, going forward to the different assessment tools, including artificial intelligence, and the different therapeutic modalities including new therapeutic targets. Epidemiology and quality of life, along with a dedicated session for people with vitiligo, were included as well. A session for clinical cases was also held this year in which different challenging cases with vitiligo and vitiligo mimickers were presented.

Advanced melanoma is typically treated with immune checkpoint inhibitors (ICIs) and targeted therapies. However, their efficacy is limited in acral and mucosal melanomas, which are more prevalent in non-White populations and often exhibit low tumor mutational burden and lack BRAF mutations. Fusion genes, widely used as therapeutic targets in other cancers, may represent alternative targets in these melanoma subtypes. This study aimed to detect fusion genes in Japanese melanomas lacking major driver mutations (BRAF, RAS, NF1, or KIT) using a custom RNA-based anchored multiplex polymerase chain reaction (AMP) panel. RNA extracted from 14 tumors, primarily formalin-fixed paraffin-embedded specimens, was analyzed using a custom Archer FUSIONPlex panel. Libraries were successfully generated in 80% of cases, and two in-frame fusions—MAD1L1::BRAF and CIC::MEGF8—were identified (17%). MAD1L1::BRAF retained the BRAF kinase domain and may be targetable by MEK inhibitors. CIC::MEGF8, a novel fusion in melanoma, may result in transcriptional dysregulation through CIC loss of function. This Method paper outlines the AMP workflow, including troubleshooting strategies and quality control criteria, and demonstrates its applicability to clinical samples. Our findings support the utility of RNA-based fusion detection in driver-negative melanomas and the potential of fusion genes as actionable targets.

Melasma, a refractory hyperpigmentation disorder, requires noninvasive tools for accurate pathological assessment. This study compared two-photon microscopy (TPM) and reflectance confocal microscopy (RCM) for the in vivo characterization of melasma pathology. In this cross-sectional study, TPM and RCM features and imaging clarity were evaluated in 130 melasma patients. Spearman correlation analyses were performed between TPM-quantified epidermal melanin, the melanin index (MI), and the individual typology angle (ITA). Features were also compared between active and stable disease stages. TPM and RCM showed substantial agreement in detecting increased epidermal melanin (κ = 0.651), activated melanocytes at the dermal-epidermal junction (DEJ) (κ = 0.711), and flattened rete ridges (κ = 0.691) (all p < 0.001). TPM excelled in visualizing intracellular melanin distribution, pendulous melanocytes under the DEJ, and solar elastosis, while RCM better identified activated melanocytes at the DEJ. TPM-quantified epidermal melanin content correlated positively with MI and negatively with ITA. RCM-detected dermal inflammatory cells were more prevalent in active than in stable melasma. In conclusion, TPM and RCM synergistically capture critical melasma features, with TPM assessing disease severity via epidermal melanin quantification, whereas RCM reflects disease activity by detecting inflammatory cells. This provides clinicians with tailored imaging tools for precision management.

The diagnostic approaches for Hermansky-Pudlak Syndrome (HPS) include genetic sequencing, immunoblotting, electron microscopy (EM), and flow cytometry with mepacrine staining. However, these methods are often impractical for routine clinical use due to high cost, technical complexity, and limited availability. In this study, we evaluated dense granules (DGs) function in HPS mouse models using flow cytometry with mepacrine and FluoZin-3 staining. We then developed a standardized, practical flow cytometry-based protocol and validated it in patients with HPS and oculocutaneous albinism (OCA), which were confirmed by whole-mount EM. In HPS mouse models (BLOC-1, BLOC-2, BLOC-3, and AP-3 deficient mutants), mepacrine uptake was consistently reduced. FluoZin-3 fluorescence showed subtype-specific zinc dysregulation, with elevated levels in BLOC-1, BLOC-2, and AP-3 mutants but decreased levels in the BLOC-3 mutant. In contrast, the OCA-6 mouse mutant showed no significant changes in either mepacrine or FluoZin-3 uptake. Similar patterns were observed in HPS and non-syndromic OCA patients. Our findings indicate that the protocol can enable the precise diagnosis and preliminary subtype classification of HPS, while also facilitating differential diagnosis between HPS and OCA. This method offers a rapid, clinically accessible alternative to conventional diagnostic techniques and may also be applicable to other storage pool disorders with DG defects.

The term acquired dermal macular hyperpigmentation (ADMH) was introduced to unify Riehl's melanosis (RM), lichen planus pigmentosus (LPP), and related entities. These are cosmetically distressing pigmentary disorders that pose therapeutic challenges. To investigate the efficacy and safety of oral isotretinoin in treating ADMH, we conducted a muticenter retrospective study of patients with ADMH treated with oral isotretinoin between 2014 and 2024. Patients from Australia, China, Europe, India, Middle East, North America, and North Africa were included. Patients lost to follow-up before two visits were excluded. The response was graded by a 5-point Investigator's Global Assessment (IGA) scale. A total of 121 patients were included. Most patients (64.5%) were treated with a dose of 20 mg/d for an average of 8 months. Oral isotretinoin improved the severity of pigmentation in all RM and 85 (90.4%) LPP patients, with 17 (63.0%) RM and 31 (33.0%) LPP patients achieving marked improvement. RM patients responded better than LPP patients (p = 0.005). Patients with localized lesions (p = 0.0012), disease duration of less than 5 years (p = 0.046 for RM, p = 0.0272 for LPP), Fitzpatrick skin phototypes III-VI (p = 0.0081), or longer duration of treatment (p = 0.0178) responded better. Oral isotretinoin appears to be a promising treatment modality for ADMH.