Frequent MAGE Mutations in Human Melanoma
Frequent MAGE Mutations in Human Melanoma
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DOI：
10.1371/journal.pone.0012773
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发表时间：
2010-09-16
期刊：
影响因子：
3.7
通讯作者：
Simpson, Andrew J.
中科院分区：
文献类型：
--
作者：
Caballero, Otavia L.;Zhao, Qi;Simpson, Andrew J.
背景资料：癌症/睾丸（CT）基因仅在生殖系和某些肿瘤中表达，并且最常位于X染色体上（CT-X基因）。在研究得最好的CT-X基因中，有编码几个法师蛋白家族的基因。法师蛋白质的功能还没有很好地理解，但有几个已被证明可能会影响致瘤性phenotype.Methodology/主要调查结果：我们进行了突变分析的编码区的四个CT-X法师基因，MAGEA 1，MAGEA 4，MAGEC 1，MAGEC 2和无处不在的表达MAGEE 1在人类黑色素瘤样本。我们首先检查了从肿瘤中建立的细胞系和27名黑色素瘤患者的匹配血液样本。我们发现，37%的患者的黑色素瘤细胞系含有至少一个突变的法师基因。单个法师基因编码区的突变频率从MAGEA 1和MAGEA 4的3.7%到MAGEC 2的14.8%不等。我们还检查了从86名患者中收集的111份新鲜黑色素瘤样本。在这种情况下，来自32%的患者的样品显示出一个或多个法师基因的突变，单个法师基因的突变频率范围从MAGEA 1的6%到MAGE EC 1的16%。意义：这些结果首次证明法师基因家族在黑素瘤中频繁突变。
Background: Cancer/testis (CT) genes are expressed only in the germ line and certain tumors and are most frequently located on the X-chromosome (the CT-X genes). Amongst the best studied CT-X genes are those encoding several MAGE protein families. The function of MAGE proteins is not well understood, but several have been shown to potentially influence the tumorigenic phenotype.Methodology/Principal Findings: We undertook a mutational analysis of coding regions of four CT-X MAGE genes, MAGEA1, MAGEA4, MAGEC1, MAGEC2 and the ubiquitously expressed MAGEE1 in human melanoma samples. We first examined cell lines established from tumors and matching blood samples from 27 melanoma patients. We found that melanoma cell lines from 37% of patients contained at least one mutated MAGE gene. The frequency of mutations in the coding regions of individual MAGE genes varied from 3.7% for MAGEA1 and MAGEA4 to 14.8% for MAGEC2. We also examined 111 fresh melanoma samples collected from 86 patients. In this case, samples from 32% of the patients exhibited mutations in one or more MAGE genes with the frequency of mutations in individual MAGE genes ranging from 6% in MAGEA1 to 16% in MAGEC1.Significance: These results demonstrate for the first time that the MAGE gene family is frequently mutated in melanoma.