Absence of AKT1 Mutations in Glioblastoma
Absence of AKT1 Mutations in Glioblastoma
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DOI：
10.1371/journal.pone.0005638
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发表时间：
2009-05-20
期刊：
影响因子：
3.7
通讯作者：
Bardelli, Alberto
中科院分区：
文献类型：
--
作者：
Bleeker, Fonnet E.;Lamba, Simona;Bardelli, Alberto
背景：PI 3 K信号通路的致癌激活在多形性胶质母细胞瘤（GBM）的发展中起着关键作用。PI 3 K下游信号传导的中心节点由丝氨酸-苏氨酸激酶AKT 1控制。最近在乳腺癌和结肠癌中发现了影响AKT 1基因残基E17的体细胞突变。E17 K变化导致组成性AKT 1活化，诱导小鼠白血病，因此，可以在治疗上用于靶向PI 3 K通路。评估AKT 1是否被激活的体细胞突变GBM是相关的，以建立其在这种侵略性diseases.Methodology/主要结果的作用：我们进行了系统的突变分析的AKT 1基因的完整编码序列在一个面板的109个肿瘤GBM样本和9个高级别星形细胞瘤细胞系。结论：我们的数据表明，在GBM中，PI 3 K通路的致癌失调并不涉及AKT 1编码区的体细胞突变。
Background: Oncogenic activation of the PI3K signalling pathway plays a pivotal role in the development of glioblastoma multiforme (GBM). A central node in PI3K downstream signalling is controlled by the serine-threonine kinase AKT1. A somatic mutation affecting residue E17 of the AKT1 gene has recently been identified in breast and colon cancer. The E17K change results in constitutive AKT1 activation, induces leukaemia in mice, and accordingly, may be therapeutically exploited to target the PI3K pathway. Assessing whether AKT1 is activated by somatic mutations in GBM is relevant to establish its role in this aggressive disease.Methodology/Principal Findings: We performed a systematic mutational analysis of the complete coding sequence of the AKT1 gene in a panel of 109 tumor GBM samples and nine high grade astrocytoma cell lines. However, no somatic mutations were detected in the coding region of AKT1.Conclusions/Significance: Our data indicate that in GBM oncogenic deregulation of the PI3K pathway does not involve somatic mutations in the coding region of AKT1.