Matsumoto Hayato, Nagano Hiromi, Kyutoku Takayuki, Yamashita Masaru
Department of Otolaryngology Head and Neck Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Laryngoscope. 2025 Jan;135(1):134-139. doi: 10.1002/lary.31676. Epub 2024 Aug 9.
The purpose of this study is to compare genetic mutations, tumor mutation burden (TMB), and the effects of molecular targeted drugs and immune checkpoint inhibitors (ICIs) in head and neck mucosal melanoma (HNMUM) with those in skin melanoma (SKM) and ocular melanoma (OM).
Data were analyzed for 72 consecutive patients with HNMUM, including 366 with SKM and 31 with OM, registered at the Japan National Cancer Center, Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 2019 and October 2023. Genetic alterations and TMB were determined by FoundationOne CDx next-generation sequencing.
The top 10 mutations in HNMUM were RAD21 (47.2%), NBN (45.8%), MYC (40.3%), LYN (31.9%), NRAS (29.1%), IRF4 (23.6%), DAXX (22.2%), KIT (22.2%), NOTCH3 (20.8%), and DDR1 (19.4%), with 16.6 ± 0.8 (mean ± SEM) mutations/individual. In SKM, BRAF (p = 0.04) mutation was associated with a significantly better prognosis. The TMB values were 5.7 ± 2.1 (mean ± SEM) in HNMUM, 4.1 ± 0.2 in SKM, and 3.4 ± 0.9 in OM, with no significant differences among the three groups. The median survival time for patients with distant metastases was 803 (95% confidence interval: 539-NA) days for HNMUM, 1413 (831-2172) days for SKM, and 1138 (438-NA) days for OM.
The top 10 mutations in HNMUM are closer to those in OM than those in SKM. There was no significant difference in TMB values or survival rates with regard to the therapeutic effect of ICIs among the diseases, which suggests that current treatment of HNMUM with ICIs is appropriate.
3 Laryngoscope, 135:134-139, 2025.
本研究旨在比较头颈部黏膜黑色素瘤（HNMUM）与皮肤黑色素瘤（SKM）和眼部黑色素瘤（OM）的基因突变、肿瘤突变负荷（TMB）以及分子靶向药物和免疫检查点抑制剂（ICI）的疗效。
分析了2019年6月至2023年10月期间在日本国立癌症中心癌症基因组学与先进治疗中心（C-CAT）登记的72例连续HNMUM患者的数据，包括366例SKM患者和31例OM患者。通过FoundationOne CDx下一代测序确定基因改变和TMB。
HNMUM的前10大突变是RAD21（47.2%）、NBN（45.8%）、MYC（40.3%）、LYN（31.9%）、NRAS（29.1%）、IRF4（23.6%）、DAXX（22.2%）、KIT（22.2%）、NOTCH3（20.8%）和DDR1（19.4%），个体平均突变数为16.6±0.8（均值±标准误）。在SKM中，BRAF（p = 0.04）突变与显著更好的预后相关。HNMUM的TMB值为5.7±2.1（均值±标准误），SKM为4.1±0.2，OM为3.4±0.9，三组之间无显著差异。远处转移患者的中位生存时间，HNMUM为803天（95%置信区间：539 - 无上限），SKM为1413天（831 - 2172天），OM为1138天（438 - 无上限）。
HNMUM的前10大突变与OM的更接近，而与SKM的差异较大。在疾病之间，ICI治疗效果的TMB值或生存率无显著差异，这表明目前用ICI治疗HNMUM是合适的。
3《喉镜》，135:134 - 139，2025年。
