迄今为止，关于粘膜黑色素瘤（MM）的靶向治疗疗效的数据是有限的。本研究分析了根据起源部位的遗传异常，这可能为MM的靶向治疗提供线索。我们进行了一项回顾性队列研究，纳入了112例MM患者。使用靶向测序分析了基因异常。采用Kaplan-Meier分析和log-rank检验比较亚组之间的显著性。 总共纳入了112例根据解剖部位分布的MM患者：头颈部38例（33.9%），泌尿生殖道22例（19.6%），直肠21例（18.8%），食管19例（17.0%），眼脏10例（8.9%），小肠2例（1.8%）。最显著的突变基因包括BRAF（17%），KIT（15%），RAS（15%），TP53（13%），NF1（12%），SF3B1（11%），GNA11（7%），GNAQ（5%）和FBXW7（4%）。发现了大量的染色体结构变异。食管和小肠的解剖部位是进展无病生存期（PFS，风险比[HR] 4.78，95%置信区间[CI] 2.42-9.45，P < 0.0001）和总生存期（OS，HR 5.26，95% CI 2.51-11.03，P < 0.0001）的独立风险因素。Casitas-B系列淋巴瘤（CBL）突变体的PFS和OS较差。相反，接受免疫检查点抑制剂（ICIs）治疗的MM患者的OS较好（HR 0.39，95% CI 0.20-0.75，P = 0.008）。 我们的发现揭示了MM患者的遗传特征，主要涉及六个解剖部位，为靶向治疗提供了潜在途径。 © 2023 BioMed Central有限公司，施普林格自然出版集团的一部分。

To date, data on the efficacy of targeted therapies for mucosal melanoma (MM) are limited. In this study, we analyzed genetic alterations according to the primary site of origin, which could provide clues for targeted therapy for MM.We conducted a retrospective cohort study of 112 patients with MM. Targeted sequencing was performed to analyze genetic aberrations. Kaplan-Meier analysis was conducted with the log-rank test to compare the significance among subgroups.In total, 112 patients with MM were included according to the anatomic sites: 38 (33.9%) in the head and neck, 22 (19.6%) in the genitourinary tract, 21 (18.8%) in the anorectum, 19 (17.0%) in the esophagus, 10 (8.9%) in the uvea, and 2 (1.8%) in the small bowel. The most significantly mutated genes included BRAF (17%), KIT (15%), RAS (15%), TP53 (13%), NF1 (12%), SF3B1 (11%), GNA11 (7%), GNAQ (5%), and FBXW7 (4%). A large number of chromosomal structural variants was found. The anatomic sites of esophagus and small bowel were independent risk factors for progression-free survival (PFS, hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.42-9.45, P < 0.0001) and overall survival (OS, HR 5.26, 95% CI 2.51-11.03, P < 0.0001). Casitas B-lineage lymphoma (CBL) mutants showed significantly poorer PFS and OS. In contrast, MM patients who received immune checkpoint inhibitors (ICIs) had a significantly more favorable OS (HR 0.39, 95% CI 0.20-0.75, P = 0.008).Our findings reveal the genetic features of patients with MM, mainly across six anatomic sites, offering a potential avenue for targeted therapies.© 2023. BioMed Central Ltd., part of Springer Nature.