Institute of Pathology, University Medicine Rostock, Strempelstraße 14, 18055, Rostock, Germany.
Department of Ophthalmology, University Medicine Rostock, Rostock, Germany.
Pathol Oncol Res. 2019 Oct;25(4):1319-1325. doi: 10.1007/s12253-017-0371-7. Epub 2017 Dec 5.
Malignant melanoma of the uvea is the most common primary malignant tumor in the eye. We aimed to analyze GNAQ and GNA11 mutations in uveal melanomas using formalin-fixed, paraffin-embedded material and correlate the results with clinicopathological parameters. Tumor tissue was microdissected followed by amplification of GNAQ exon 4 and 5, GNA11 exon 4 and 5, and finally analyzed by Sanger sequencing. A total of 64.4 GNA11/GNAQ mutations, including ten yet unreported, were found. Two cases showed multiple mutations. Overall survival was significantly shorter in the uveal melanoma cohort with GNAQ exon 5 mutation. In concordance with previous studies, high frequencies of mutations in GNAQ or GNA11 were detected. Interestingly, in about 20% of UM, not yet reported mutations in GNAQ or GNA11 were seen. Rarely, uveal melanoma may harbor double mutations in GNAQ and/or GNA11. Recent data imply, that implementation of GNAQ/GNA11 mutation analysis in routine diagnostic procedures might be helpful for future therapeutic decisions.
葡萄膜恶性黑色素瘤是眼内最常见的原发性恶性肿瘤。本研究旨在使用福尔马林固定石蜡包埋（FFPE）材料分析葡萄膜黑色素瘤中的 GNAQ 和 GNA11 突变，并将结果与临床病理参数相关联。对肿瘤组织进行显微切割，然后扩增 GNAQ 外显子 4 和 5、GNA11 外显子 4 和 5，最后进行 Sanger 测序分析。共发现了 64.4 种 GNA11/GNAQ 突变，其中包括十种尚未报道的突变。两种病例显示存在多种突变。与先前的研究一致，在葡萄膜黑色素瘤队列中，GNAQ 外显子 5 突变的总生存率明显更短。与以往研究一致，检测到 GNAQ 或 GNA11 中的高频突变。有趣的是，在大约 20%的 UM 中，观察到了尚未报道的 GNAQ 或 GNA11 突变。很少情况下，葡萄膜黑色素瘤可能同时存在 GNAQ 和/或 GNA11 的双突变。最近的数据表明，在常规诊断程序中实施 GNAQ/GNA11 突变分析可能有助于未来的治疗决策。
