粘膜黑色素瘤是一种罕见的恶性肿瘤；然而，据报道，亚洲人粘膜黑色素瘤的发病率高于白种人。鼻窦粘膜黑色素瘤（SNMM）是一种侵袭性恶性肿瘤，由于远处转移，预后较差。 BRAF抑制剂和MEK抑制剂的全身治疗是具有BRAF V600突变的皮肤黑色素瘤患者的护理标准之一。然而，尚未建立针对粘膜黑色素瘤患者的分子靶向治疗。由于其频率较低，相对较少的研究描述了与粘膜黑色素瘤相关的基因突变。此外，据我们所知，日本患者的基因突变尚未见报道。因此，在本研究中，我们评估了SNMM患者的遗传和临床病理特征。基于靶向二代测序，对从SNMM患者获得的总共18份组织样本进行基因突变分析，以探讨肿瘤发生的驱动因素和/或用于预测 SNMM 临床结果的候选基因。我们还对发现 CTNNB1 突变的患者进行了免疫组织化学检查。18 名患者中有 8 名 (44%) 患有基因突变。最常见的突变是 NRAS（6/18，33%），其次是 CTNNB1（2/18，11%）和 BRAF（1/18，5.6%）。一名患者同时患有 NRAS 和 CTNNB1 突变。有和没有基因突变的患者的临床结果没有显着差异。 NRAS 突变与相对较高的 T 分类和较差的生存率相关，但差异并不显着。在两个具有 CTNNB1 突变的肿瘤中均检测到 β-连环蛋白的核转位。 BRAF突变的氨基酸变化为外显子15中的K601R。在目前的研究中，未检测到BRAF V600突变。基因突变与临床结果没有显着相关性。然而，NRAS 突变可能是预后预测因子，CTNNB1 突变可能是免疫检查抑制剂的治疗效应因子。需要进行更大规模的前瞻性研究来阐明 SNMM 患者基因突变的临床重要性。版权所有 © 2023。由 Elsevier B.V. 出版。

Mucosal melanoma is a rare malignancy; however, the reported incidence rate of mucosal melanoma is higher in Asians than in Caucasians. Sinonasal mucosal melanoma (SNMM) is an aggressive malignancy with a poor prognosis due to distant metastasis. Systemic therapy with BRAF inhibitor and MEK inhibitor is one of the standards of care for cutaneous melanoma patients with BRAF V600 mutations. However, no molecular targeted therapy for patients with mucosal melanoma has been established. Relatively few studies have described the genetic mutations associated with mucosal melanoma because of its low frequency. Furthermore, to the best of our knowledge, the genetic mutations among Japanese patients have not been reported. Therefore, in the current study, we evaluated the genetic and clinicopathological characteristics of patients with SNMM.A total of 18 tissue samples obtained from patients with SNMM were analyzed for genetic mutations based on targeted next-generation sequencing to investigate the driver of tumorigenesis and/or candidate genes for predicting clinical outcomes in SNMM. We also performed immunohistochemistry for patients identified with CTNNB1 mutations.Eight of the 18 (44 %) patients had genetic mutations. The most frequent mutation was NRAS (6/18, 33 %), followed by CTNNB1 (2/18, 11 %) and BRAF (1/18, 5.6 %). One patient had both NRAS and CTNNB1 mutations. Clinical outcomes did not differ significantly between those with and without genetic mutations. NRAS mutations were associated with relatively higher T classification and worse survival rates, although the differences were not significant. The nuclear translocation of β-catenin was detected in both tumors with CTNNB1 mutations. The amino acid change in the BRAF mutation was K601R in exon 15. In the current study, no BRAF V600 mutations were detected.Genetic mutations were not significantly associated with clinical outcomes. However, NRAS mutations may be a prognostic predictor and CTNNB1 mutation may be a treatment effector for immune check inhibitors. A larger prospective study is required to clarify the clinical importance of genetic mutations in patients with SNMM.Copyright © 2023. Published by Elsevier B.V.