Detection of the transforming AKT1 mutation E17K in non-small cell lung cancer by high resolution melting.
Detection of the transforming AKT1 mutation E17K in non-small cell lung cancer by high resolution melting.
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DOI：
10.1186/1756-0500-1-14
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发表时间：
2008-05-16
影响因子：
1.8
通讯作者：
Dobrovic A
中科院分区：
文献类型：
--
作者：
Do H;Solomon B;Mitchell PL;Fox SB;Dobrovic A
最近在乳腺癌、结直肠癌和卵巢癌中描述了AKT1基因的普列克底物蛋白同源结构域中的复发性体细胞突变E17 K。AKT1是参与细胞存活、增殖和生长的信号传导途径的关键介质。E17 K突变刺激下游信号传导，并在体外和体内表现出转化活性。我们开发了一种灵敏的高分辨率熔解（HRM）检测E17 K突变福尔马林固定石蜡包埋肿瘤。我们使用HRM分析筛选了219例非小细胞肺癌活检组织的突变。4份样本被鉴定为HRM阳性。随后对这些样本的测序证实了其中一例病例中的E17K突变。一个罕见的单核苷酸多态性检测在其余三个样本。E17 K在14例鳞状细胞癌中有1例阳性。在141例腺癌和39例大细胞癌中未发现突变。AKT1 E17 K突变在肺癌中非常罕见，可能与鳞状细胞癌的发生有关。HRM代表了对临床样品中的低频突变（如AKT1突变）的快速、经济和稳健的筛查。
A recurrent somatic mutation, E17K, in the pleckstrin homology domain of the AKT1 gene, has been recently described in breast, colorectal, and ovarian cancers. AKT1 is a pivotal mediator of signalling pathways involved in cell survival, proliferation and growth. The E17K mutation stimulates downstream signalling and exhibits transforming activity in vitro and in vivo. We developed a sensitive high resolution melting (HRM) assay to detect the E17K mutation from formalin-fixed paraffin-embedded tumours. We screened 219 non-small cell lung cancer biopsies for the mutation using HRM analysis. Four samples were identified as HRM positive. Subsequent sequencing of those samples confirmed the E17K mutation in one of the cases. A rare single nucleotide polymorphism was detected in each of the remaining three samples. The E17K was found in one of the 14 squamous cell carcinomas. No mutations were found in 141 adenocarcinomas and 39 large cell carcinomas. The AKT1 E17K mutation is very rare in lung cancer and might be associated with tumorigenesis in squamous cell carcinoma. HRM represents a rapid cost-effective and robust screening of low frequency mutations such as AKT1 mutations in clinical samples.