Eye Pathology Section, Department of Pathology.
Department of Ophthalmology, Rigshospitalet, Copenhagen University Hospital, Copenhagen.
Melanoma Res. 2020 Dec;30(6):533-542. doi: 10.1097/CMR.0000000000000686.
Herein, we wanted to explore the molecular landscape of mucosal melanoma from different sites and identify potential molecular targets for future therapy. Mucosal melanomas (N = 40) from different sites (conjunctiva, sinonasal cavity, rectum, and vagina) were investigated. Targeted next-generation sequencing along with Nanostring gene expression profiling was performed. Genetically, conjunctival melanoma was characterized by BRAF-V600E (30%) and NF1 mutations (17%). Mucosal melanomas at nonsun-exposed sites harbored alterations in NRAS, KIT, NF1, along with atypical BRAF mutations. When comparing the gene expression profile of conjunctival melanoma and nonsun-exposed mucosal melanoma, 41 genes were found to be significantly deregulated. Programmed death-ligand 1 (PD-L1) presented a significant sixfold upregulation in conjunctival melanoma compared to the other mucosal melanomas. While melanomas of the sinonasal cavity, vagina, and rectum are molecularly similar, conjunctival melanoma is characterized by a higher frequency of BRAF-V600E mutations and differential expression of several genes involved in the immune response.
在这里,我们希望探索来自不同部位的黏膜黑色素瘤的分子特征,并确定未来治疗的潜在分子靶点。研究了来自不同部位(结膜、鼻腔鼻窦、直肠和阴道)的黏膜黑色素瘤(N=40)。进行了靶向下一代测序和 Nanostring 基因表达谱分析。从遗传学角度来看,结膜黑色素瘤的特征是 BRAF-V600E(30%)和 NF1 突变(17%)。非阳光暴露部位的黏膜黑色素瘤存在 NRAS、KIT、NF1 改变以及非典型 BRAF 突变。当比较结膜黑色素瘤和非阳光暴露黏膜黑色素瘤的基因表达谱时,发现有 41 个基因明显失调。与其他黏膜黑色素瘤相比,结膜黑色素瘤中程序性死亡配体 1(PD-L1)的表达显著上调了六倍。虽然鼻腔鼻窦、阴道和直肠的黑色素瘤在分子上相似,但结膜黑色素瘤的特点是 BRAF-V600E 突变频率更高,以及参与免疫反应的几个基因的差异表达。