目的:口腔粘膜黑色素瘤(OMM)是一种罕见但侵袭性的黑色素瘤亚型。由于它的稀有性,尽管对皮肤黑色素瘤(CM)的遗传特征有相对透彻的了解,但OMM的基因组景观仍然未知。在这项研究中,我们分析了日本OMM患者的基因组突变谱,并将其与鼻/窦粘膜黑色素瘤(NMM)和CM患者的基因组突变谱进行了比较,以确定潜在的治疗靶点.
方法:我们提取了OMM患者的临床和基因组信息(n=15),NMM(n=63),和CM(n=413),他们在2019年6月至2023年11月期间从癌症基因组学和治疗学中心数据库接受了国家健康保险下的全面基因组分析测试。
结果:在OMM中发现的最常见的基因组改变是RICTOR(40%),其次是CDK4(33.3%)。MDM2(33.3%),KDR(30%),KIT(26.7%),和NF1(26.7%)。CDK4和MDM2共扩增。MYC和NRAS的基因改变在NMM患者中最高,其次是那些有CM的人,在OMM患者中未观察到MYC改变。BRAFV600突变,在CM患者(23.2%)中经常观察到,仅在1.6%的NMM患者中存在,在OMM患者中没有。
结论:这项研究阐明了OMM和NMM之间的遗传差异,并首次报道了OMM中RICTOR扩增的频繁发生。该分析提供了对OMM个性化疗法开发的见解。
OBJECTIVE: Oral mucosal melanoma (OMM) is a rare but aggressive melanoma subtype. Due to its rarity, the genomic landscape of OMM remains unknown despite a relatively thorough understanding of the genetic profile of cutaneous melanoma (CM). In this study, we analyzed the genomic mutational profiles of Japanese patients with OMM and compared them with those of patients with nose/sinuses mucosal melanoma (NMM) and CM to identify potential therapeutic targets.
METHODS: We extracted clinical and genomic information of patients with OMM (n = 15), NMM (n = 63), and CM (n = 413) who underwent comprehensive genomic profiling tests under the National Health Insurance between June 2019 and November 2023 from the Center for Cancer Genomics and Therapeutics database.
RESULTS: The most frequent genomic alteration identified in OMM was RICTOR (40%) followed by CDK4 (33.3%), MDM2 (33.3%), KDR (30%), KIT (26.7%), and NF1 (26.7%). CDK4 and MDM2 were co-amplified. Gene alterations in MYC and NRAS were the highest in patients with NMM, followed by those with CM, and no MYC alteration was observed in patients with OMM. BRAF V600 mutation, which is frequently observed in patients with CM (23.2%) were only present in 1.6% of patients with NMM and none in patients with OMM.
CONCLUSIONS: This study clarified the genetic differences between OMM and NMM, and the first to report the frequent occurrence of RICTOR amplification in OMM. This analysis offers insights into the development of personalized therapeutics for OMM.