Novel somatic mutations in heterotrimeric G proteins in melanoma
Novel somatic mutations in heterotrimeric G proteins in melanoma
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DOI：
10.4161/cbt.10.1.11949
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发表时间：
2010-07-01
影响因子：
3.6
通讯作者：
Samuels, Yardena
中科院分区：
文献类型：
--
作者：
Cardenas-Navia, L. Isabel;Cruz, Pedro;Samuels, Yardena
异三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）介导G蛋白偶联受体及其下游通路之间的信号，并已被证明在癌症中发生突变。特别是，GNAQ在皮肤的蓝色痣和葡萄膜黑色素瘤中经常发生突变，以突变形式发挥致癌基因的作用。为了进一步研究异三聚体G蛋白在黑色素瘤中的作用，我们对80个黑色素瘤样本的异三聚体G蛋白基因家族中的35个基因进行了全面的突变分析。在跨越7个基因的17%的样本中检测到G蛋白亚基的体细胞改变。在GNG10和GNAZ中发现了最高的体细胞非同义突变率，这两种突变在黑色素瘤中都没有被报道过。我们的研究首次系统分析了黑色素瘤中的异源三聚体G蛋白，并表明多种异源三聚体G蛋白突变可能参与黑色素瘤的进展。
Heterotrimeric guanine nucleotide-binding proteins (G proteins) mediate signals between G-protein coupled receptors and their downstream pathways, and have been shown to be mutated in cancer. In particular, GNAQ was found to be frequently mutated in blue nevi of the skin and uveal melanoma, acting as an oncogene in its mutated form. To further examine the role of heterotrimeric G proteins in melanoma, we performed a comprehensive mutational analysis of the 35 genes in the heterotrimeric G protein gene family in a panel of 80 melanoma samples. Somatic alterations in a G protein subunit were detected in 17% of samples spanning seven genes. The highest rates of somatic, non-synonymous mutations were found in GNG10 and GNAZ, neither of which has been previously reported to be mutated in melanoma. Our study is the first systematic analysis of the heterotrimeric G proteins in melanoma and indicates that multiple mutated heterotrimeric G proteins may be involved in melanoma progression.