目的:本研究的目的是比较基因突变,肿瘤突变负荷(TMB),以及分子靶向药物和免疫检查点抑制剂(ICIs)在头颈部粘膜黑色素瘤(HNMUM)以及皮肤黑色素瘤(SKM)和眼部黑色素瘤(OM)中的作用。
方法:分析72例HNMUM患者的数据,包括带有SKM的366和带有OM的31,在日本国立癌症中心注册,癌症基因组学和高级治疗学中心(C-CAT),2019年6月至2023年10月。通过FoundationOneCDx下一代测序确定遗传改变和TMB。
结果:HNMUM的前10个突变是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%),具有16.6±0.8(平均值±SEM)突变/个体。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(平均值±SEM),SKM中的4.1±0.2,和3.4±0.9的OM,三组间无显著差异。对于HNMUM,远处转移患者的中位生存时间为803(95%置信区间:539-NA)天,SKM的1413(831-2172)天,OM为1138(438-NA)天。
结论:HNMUM的前10个突变比SKM更接近OM。关于ICIs在疾病中的治疗效果,TMB值或生存率没有显着差异,这表明目前用ICIs治疗HNMUM是合适的。
方法:3喉镜,2024.
OBJECTIVE: 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).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 3 Laryngoscope, 2024.