Toomey Christopher B, Fraser Kyle, Thorson John A, Goldbaum Michael H, Lin Jonathan H
Department of Ophthalmology, UC San Diego, La Jolla, California, USA.
VA San Diego Healthcare System, San Diego, California, USA.
Ocul Oncol Pathol. 2019 Jun;5(4):267-272. doi: 10.1159/000495508. Epub 2019 Jan 10.
G protein mutations are common in uveal melanomas, and the vast majority target amino acid residue Q209 in either GNAQ or GNA11. The GNAQ R183Q mutation is found in a small fraction of uveal melanomas. We report a patient with an unusual presentation of uveal melanoma arising at an early age in the setting of congenital skin and ocular surface melanosis. A 34-year-old Hispanic female with congenital bilateral nevus of Ota and ocular surface melanosis presented with progressive loss of visual acuity and was found to have a juxtapapillary uveal melanoma. She was treated with brachytherapy, but the tumor relapsed. She underwent enucleation that revealed mixed spindle and epithelioid uveal melanoma cells with no extraocular or lymphovascular spread. Next-generation sequencing performed on DNA isolated from the enucleation specimen identified a GNAQ R183Q mutation and a PMS1 truncation mutation. Cytogenetic profiling revealed no monosomy 3. These findings raise the possibility that uveal melanomas bearing G protein R183 mutations may have distinct clinicopathologic profiles compared to those with Q209 mutations. Furthermore, this is the first reported case of a mutation in the mismatch repair gene associated with uveal melanoma.
G蛋白突变在葡萄膜黑色素瘤中很常见，绝大多数靶向GNAQ或GNA11中的氨基酸残基Q209。GNAQ R183Q突变在一小部分葡萄膜黑色素瘤中被发现。我们报告了一名葡萄膜黑色素瘤患者，其在先天性皮肤和眼表黑色素沉着的背景下早年发病，表现不寻常。一名34岁患有先天性双侧太田痣和眼表黑色素沉着的西班牙裔女性，出现视力进行性丧失，被发现患有视乳头旁葡萄膜黑色素瘤。她接受了近距离放射治疗，但肿瘤复发。她接受了眼球摘除术，结果显示为混合性梭形和上皮样葡萄膜黑色素瘤细胞，无眼外或淋巴管扩散。对从眼球摘除标本中分离的DNA进行的二代测序确定了一个GNAQ R183Q突变和一个PMS1截短突变。细胞遗传学分析未发现三体3。这些发现增加了与携带Q209突变的葡萄膜黑色素瘤相比，携带G蛋白R183突变的葡萄膜黑色素瘤可能具有不同临床病理特征的可能性。此外，这是首次报道的与葡萄膜黑色素瘤相关的错配修复基因突变病例。
