胶质母细胞瘤中不存在AKT1突变。
Absence of AKT1 mutations in glioblastoma.
作者信息
Bleeker Fonnet E, Lamba Simona, Zanon Carlo, van Tilborg Angela A, Leenstra Sieger, Troost Dirk, Hulsebos Theo, Vandertop W Peter, Bardelli Alberto
机构信息
Neurosurgical Center Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
出版信息
PLoS One. 2009 May 20;4(5):e5638. doi: 10.1371/journal.pone.0005638.
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.
背景
PI3K信号通路的致癌激活在多形性胶质母细胞瘤（GBM）的发展中起关键作用。PI3K下游信号传导的一个中心节点由丝氨酸 - 苏氨酸激酶AKT1控制。最近在乳腺癌和结肠癌中发现了影响AKT1基因E17位点的体细胞突变。E17K变化导致AKT1组成性激活，在小鼠中诱发白血病，因此，可能在治疗上用于靶向PI3K途径。评估GBM中AKT1是否通过体细胞突变激活对于确定其在这种侵袭性疾病中的作用至关重要。
方法/主要发现：我们对109个肿瘤性GBM样本和9个高级别星形细胞瘤细胞系组成的样本组中的AKT1基因完整编码序列进行了系统的突变分析。然而，在AKT1的编码区域未检测到体细胞突变。
结论/意义：我们的数据表明，在GBM中，PI3K途径的致癌失调不涉及AKT1编码区域的体细胞突变。
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