The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non‐cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture‐based next‐generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm‐level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non‐cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFRα) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.

Objective Objective: To verrify the anti-tumor effi cacy and toxicity between juglone (Jug) and Jug-loaded : To verrify the anti-tumor effi cacy and toxicity between juglone (Jug) and Jug-loaded PLGA nanoparticles (Jug-PLGA-NPs). PLGA nanoparticles (Jug-PLGA-NPs). Methods Methods: Jug-PLGA-NPs were prepared by ultrasonic emulsification.: Jug-PLGA-NPs were prepared by ultrasonic emulsification. The anti-tumor activity of Jug (2, 3, 4 μg/mL) and Jug-PLGA-NPs (Jug: 2, 3, 4 μg/mL) The anti-tumor activity of Jug (2, 3, 4 μg/mL) and Jug-PLGA-NPs (Jug: 2, 3, 4 μg/mL) in vitro in vitro was measured was measured by MTT assay and cell apoptosis analysis. The distribution, anti-tumor effect and biological safety by MTT assay and cell apoptosis analysis. The distribution, anti-tumor effect and biological safety in vivo in vivo was was evaluated on A375 nude mice. evaluated on A375 nude mice. Results Results: With the advantage of good penetration and targeting properties, : With the advantage of good penetration and targeting properties, Jug-PLGA-NPs significantly inhibited proliferation and migration of melanoma cells both Jug-PLGA-NPs significantly inhibited proliferation and migration of melanoma cells both in vitro in vitro and and in vivo in vivo (P<0.05 or <0.05 or P<0.01) with acceptable biocompatibility. <0.01) with acceptable biocompatibility. Conclusions Conclusions: Jug can inhibit the growth of melanoma but : Jug can inhibit the growth of melanoma but is highly toxic. With the advantage of sustained release, tumor targeting, anti-tumor activity and acceptable is highly toxic. With the advantage of sustained release, tumor targeting, anti-tumor activity and acceptable biological safety, Jug-PLGA-NPs provide a new pharmaceutical form for future application of Jug. biological safety, Jug-PLGA-NPs provide a new pharmaceutical form for future application of Jug.

Background Acral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment of AM patients to gain insights into disease characteristics and potential treatment strategies. Methods A total of 90 AM patients were enrolled and their tissue samples were subjected to next-generation sequencing and multiplexed immunohistochemistry tests. Kaplan–Meier curves and log-rank tests were used to analyze the prognostic potential of various genetic aberrations and immune cell compositions in AM. Results The median disease-free survival was 21.3 months and estimated median overall survival (OS) was 60 months. More advanced stages, older ages and thickness of greater than 4 mm were associated with worse prognosis in AM patients (HR = 2.57, 95% CI 1.25–5.29, p = 0.01; HR = 2.77, 95% CI 1.22–6.28, p = 0.02; HR = 3.43, 95% CI 1.51–7.82, p < 0.01, respectively), while patients who received post-surgical treatments had better survival (HR = 0.36, 95% CI 0.17–0.76, p = 0.01). The most frequently altered genes included BRAF (14.5%), KIT (16.9%), NRAS (12%), NF1 (10.8%), APC (7.2%), and ARID2 (6%). Copy number variations (CNV) were commonly found in CCND1 (19.3%), CDK4 (19.3%), MDM2 (14.5%) and FGF19 (12%). CDK4 amplifications was independently associated with shorter OS in AM patients (HR = 3.61, 95% CI 1.38–9.46, p = 0.01). CD8 + T cells (p < 0.001) and M1 macrophages (p = 0.05) were more highly enriched in the invasive margin than in the tumor center. Patients with higher levels of M1 macrophage infiltration in the invasive margin derived markedly longer OS (HR = 0.43, 95% CI 0.20–0.95, p = 0.03). Interestingly, in CDK4-amplified patients, there tended to be a low level of M1 macrophage infiltration in the invasive margin (p = 0.06), which likely explains the poor prognosis in such patients. Conclusions Our study provided a comprehensive portrait of the clinicopathological features, genetic aberrations and tumor microenvironment profiles in AM patients and identified candidate prognostic factors, which may facilitate development of additional therapeutic options and better inform clinical management of AM patients. Based on these prognostic factors, further studies should focus on enhancing the infiltration of M1 macrophages, especially in CDK4-amplified AM patients.