ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma

BreslerS.C.; WeiserD.A.; HuweP.J.; ParkJ.H.; KrytskaK.; RylesH.; LaudenslagerM.; RappaportE.F.; WoodA.C.; McGradyP.W.; HogartyM.D.; LondonW.B.; RadhakrishnanR.; LemmonM.A.; MosséY.P.

首页> 外文期刊>Cancer Cell >ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma

【24h】

ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma

机译：ALK突变赋予神经母细胞瘤差异性致癌激活和对ALK抑制疗法的敏感性。

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

Genetic studies have established anaplastic lymphoma kinase (ALK), a cell surface receptor tyrosine kinase, as a tractable molecular target in neuroblastoma. We describe comprehensive genomic, biochemical, and computational analyses of ALK mutations across 1,596 diagnostic neuroblastoma samples. ALK tyrosine kinase domain mutations occurred in 8% of samples-at three hot spots and 13minor sites-and correlated significantly with poorer survival in high- and intermediate-risk neuroblastoma. Biochemical and computational studies distinguished oncogenic (constitutively activating) from nononcogenic mutations and allowed robust computational prediction of their effects. The mutated variants also showed differential invitro crizotinib sensitivities. Our studies identify ALK genomic status as a clinically important therapeutic stratification tool in neuroblastoma and will allow tailoring of ALK-targeted therapy to specific mutations.

机译：遗传学研究已经建立了间变性淋巴瘤激酶（ALK），一种细胞表面受体酪氨酸激酶，作为神经母细胞瘤中的易处理分子靶标。我们描述了横跨1,596个诊断性神经母细胞瘤样品的ALK突变的综合基因组学，生化和计算分析。 ALK酪氨酸激酶结构域突变发生在3个热点和13个小位点的8％的样本中，并且与高危和中危神经母细胞瘤的较差生存率显着相关。生化和计算研究将致癌性（组成性激活）与非致癌性突变区分开来，并对其结果进行了有力的计算预测。突变的变体还显示出不同的克唑替尼体外敏感性。我们的研究将ALK基因组状态鉴定为神经母细胞瘤中临床上重要的治疗分层工具，并将针对特定突变量身定制针对ALK的疗法。

著录项

来源
《Cancer Cell》 |2014年第5期|共13页
作者
BreslerS.C.; WeiserD.A.; HuweP.J.; ParkJ.H.; KrytskaK.; RylesH.; LaudenslagerM.; RappaportE.F.; WoodA.C.; McGradyP.W.; HogartyM.D.; LondonW.B.; RadhakrishnanR.; LemmonM.A.; MosséY.P.;
展开▼
作者单位

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类肿瘤学;
关键词

相似文献

外文文献
中文文献
专利

1. ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma [J] . BreslerS.C., WeiserD.A., HuweP.J., Cancer Cell . 2014,第5期

机译：ALK突变赋予神经母细胞瘤差异性致癌激活和对ALK抑制疗法的敏感性。
2. Activating mutations in ALK kinase domain confer resistance to structurally unrelated ALK inhibitors in NPM-ALK-positive anaplastic large-cell lymphoma. [J] . Daria Zdzalik, Barbara Dymek, Paulina Grygielewicz, Journal of Cancer Research and Clinical Oncology . 2014,第4期

机译：ALK激酶结构域中的激活突变赋予NPM-ALK阳性间变性大细胞淋巴瘤中结构无关的ALK抑制剂耐药性。
3. Activating mutations in ALK kinase domain confer resistance to structurally unrelated ALK inhibitors in NPM-ALK-positive anaplastic large-cell lymphoma. [J] . Daria Zdzalik, Barbara Dymek, Paulina Grygielewicz, Journal of Cancer Research and Clinical Oncology . 2014,第4期

机译：碱酶结构域的激活突变在NPM-ALK阳性促进性大细胞淋巴瘤中对结构不相关的ALK抑制剂的抵抗力。
4. Functional characterization of ubiquitination profile changes induced by oncogenic protein NPM-ALK in ALK~(+) anaplastic large cell lymphoma cells [C] . Fang Wu, Peng Wang, Raymond Lai, American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics . 2010

机译：致癌蛋白NPM-ALK诱导ubiquitination曲线变化的功能表征Ala1（+）促进大细胞淋巴瘤细胞
5. Pharmacology Profiles of ALK and FLT3 Kinase Inhibitors against Non-Small-Cell Lung Cancer Cells and Acute Myeloid Leukemia Cells with Cancer Driver Mutations [D] . 森政道 2019

机译：ALK和FLT3激酶抑制剂对非小细胞肺癌细胞和急性髓系白血病细胞的癌症驱动突变的药理作用
6. ALK mutations confer differential oncogenic activation and sensitivity to ALK inhibition therapy in neuroblastoma [O] . Scott C. Bresler, Daniel A. Weiser, Peter J. Huwe, -1

机译：ALK突变赋予神经母细胞瘤不同的致癌活性和对ALK抑制疗法的敏感性
7. ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma [O] . Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA ( host institution ), Bresler, Scott C. ( author ), Weiser, Daniel A. ( author ), 2014

机译：ALK突变赋予神经母细胞瘤差异性致癌激活和对ALK抑制疗法的敏感性。

ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma

摘要

著录项

相似文献

相关主题

期刊订阅