Distribution of GNAQ and GNA11 Mutation Signatures in Uveal Melanoma Points to a Light Dependent Mutation Mechanism
Distribution of GNAQ and GNA11 Mutation Signatures in Uveal Melanoma Points to a Light Dependent Mutation Mechanism
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DOI：
10.1371/journal.pone.0138002
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发表时间：
2015-09-14
期刊：
影响因子：
3.7
通讯作者：
van der Velden, Pieter A.
中科院分区：
文献类型：
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作者：
de Lange, Mark J.;Razzaq, Lubna;van der Velden, Pieter A.
葡萄膜黑色素瘤（UM）起源于眼睛内壁中的黑色素细胞，即来自虹膜、睫状体和脉络膜，具有明显的光暴露差异（从黑暗的前部到照亮的后部）。与紫外线辐射相反，聚焦或会聚的可见光容易到达视网膜，并可能损害DNA，这可能有助于UM的发展。在这份报告中，脉络膜，睫状体脉络膜和虹膜睫状体黑色素瘤的GNAQ和GNA11突变，随后与肿瘤起源的位置进行了分析。GNAQ和GNA11中的热点突变可以分为A>T和A>C突变特征。GNAQ A626 C突变（Q209 P）几乎只在脉络膜黑色素瘤中观察到。另一方面，来自深色前侧的睫状脉络膜UM（大多数为A>T突变）与浅色眼睛明显相关。结合这些数据表明，光和色素依赖性的病因在UM的发展。
Uveal melanomas (UM) originate from melanocytes in the interior wall of the eye, namely from the iris, ciliary body and the choroid with marked differences in light exposure (from dark anterior to illuminated posterior). In contrast to UV radiation, focused or converging visible light readily reaches the retina and can damage DNA which possibly contributes to UM development. In this report choroidal, ciliochoroidal and iridociliary melanomas were analyzed for GNAQ and GNA11 mutations which were subsequently correlated to the location of tumor origin. Hotspot mutations in GNAQ and GNA11 can be divided in A>T and in A>C mutation signatures. The GNAQ A626C mutation (Q209P) was almost exclusively observed in choroidal melanomas from the illuminated posterior side. On the other hand, ciliochoroidal UM from the dark anterior side with mostly A>T mutations were clearly associated with light-colored eyes. Combined these data suggest a light and a pigment dependent etiology in UM development.