The Role of Mutation Rates of GNAQ or GNA11 in Cases of Uveal Melanoma in Japan
The Role of Mutation Rates of GNAQ or GNA11 in Cases of Uveal Melanoma in Japan
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DOI：
10.1097/pai.0000000000000505
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发表时间：
2017-02
影响因子：
1.6
通讯作者：
J. Ominato;T. Fukuchi;Ayako Sato;N. Yamaguchi;Kazue Kobayashi;Hiroyuki Cho;T. Oyama;Y. Ajioka
中科院分区：
文献类型：
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作者：
J. Ominato;T. Fukuchi;Ayako Sato;N. Yamaguchi;Kazue Kobayashi;Hiroyuki Cho;T. Oyama;Y. Ajioka
GNAQ和GNA 11突变被认为对葡萄膜黑色素瘤的肿瘤发生是重要的。虽然以前的研究报告了葡萄膜黑色素瘤病例的突变率，但目前还没有日本人群的此类报告。在这项研究中，我们研究的频率GNAQ和GNA 11体细胞突变的葡萄膜黑色素瘤的情况下，在日本和它们的关系与临床病理特征或Ki-67阳性细胞率（Ki-67标记指数：Ki-67 LI）使用免疫荧光方法。这项研究涉及19例葡萄膜黑色素瘤。我们使用DNA提取试剂盒从福尔马林固定、石蜡包埋的标本中提取模板DNA。我们使用聚合酶链反应扩增GNAQ和GNA 11的DNA序列，并通过直接测序分析突变。我们使用免疫荧光方法评估Ki-67 LI。GNAQ和GNA 11体细胞突变频率分别为26.3%（5/19）和31.6%（6/19）。GNAQ和GNA 11突变是相互排斥的，如以前的报告所示。上皮样细胞中GNA 11突变的频率显著较高;然而，GNAQ突变与细胞类型之间无明显相关性，突变阳性和突变阴性肿瘤之间Ki-67 LI无显著差异。GNAQ和GNA 11突变在日本的葡萄膜黑色素瘤病例中被鉴定，尽管频率低于白色患者。上皮样细胞GNA 11基因突变频率明显增高。
GNAQ and GNA11 mutations are thought to be important for the tumorigenesis of uveal melanoma. Although previous studies have reported on mutation rates in cases of uveal melanoma, presently, no such report for the Japanese population exists. In this study, we examined the frequency of GNAQ and GNA11 somatic mutations in cases of uveal melanoma in Japan and their relationship with clinicopathologic features or Ki-67-positive cell rates (Ki-67 labeling index: Ki-67 LI) using immunofluorescence methods. The study involved 19 cases of uveal melanoma. We extracted the template DNA from formalin-fixed, paraffin-embedded specimens using a DNA extraction kit. We amplified the DNA sequences of GNAQ and GNA11 using polymerase chain reaction and analyzed mutations by direct sequencing. We evaluated Ki-67 LI using immunofluorescence methods. The frequencies of GNAQ and GNA11 somatic mutations were 26.3% (5/19) and 31.6% (6/19), respectively. The GNAQ and GNA11 mutations were mutually exclusive, as indicated in previous reports. The frequency of GNA11 mutations was significantly higher in epithelioid cells; however, no significant association between GNAQ mutations and cell type was evident, and there was no significant difference in Ki-67 LI between the mutation-positive and mutation-negative tumors. GNAQ and GNA11 mutations were identified in cases of uveal melanoma in Japan, although at lower frequencies than in white counterparts. The mutation frequency of GNA11 was significantly higher in epithelioid cells.