Prospective, high-throughput molecular profiling of human gliomas.
Prospective, high-throughput molecular profiling of human gliomas.
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DOI：
10.1007/s11060-012-0938-9
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发表时间：
2012-10
影响因子：
3.9
通讯作者：
Iafrate, A. John
中科院分区：
文献类型：
--
作者：
Chi, Andrew S.;Batchelor, Tracy T.;Dias-Santagata, Dora;Borger, Darrell;Stiles, Charles D.;Wang, Daphne L.;Curry, William T.;Wen, Patrick Y.;Ligon, Keith L.;Ellisen, Leif;Louis, David N.;Iafrate, A. John
神经胶质瘤由多种组织学和分子亚型组成，具有不同的临床表型和对治疗的反应。然而，临床试验的入组标准在很大程度上仍然没有考虑到这些潜在的分子差异。我们已将基于 ABI SNaPshot 平台的高通量肿瘤基因分型程序以及其他分子诊断测试纳入神经胶质瘤患者的标准评估中，以评估前瞻性分子分析是否允许合理选择患者进入临床试验。我们前瞻性地从 218 个神经胶质瘤中收集了来自 15 个关键癌症基因的 68 个突变位点的 SNaPshot 基因分型数据，以及来自基因扩增（EGFR、PDGFRA、MET）、1p/19q 共缺失和 MGMT 启动子甲基化临床检测的数据。在 38.5% 和 47.1% 的胶质母细胞瘤中分别检测到 SNaPshot 突变和局灶性基因扩增。 EGFR、IDH1 和 PIK3CA 的基因改变频率与最近研究报告的频率非常匹配。此外，我们还发现了一些在神经胶质瘤中罕见的事件，尽管在其他癌症类型中是已知的驱动突变，例如 AKT1、BRAF 和 KRAS 突变。具有激活信号通路的基因改变的患者被纳入针对恶性神经胶质瘤以及其他实体癌的基因选择性临床试验。将高通量分子分析纳入神经胶质瘤患者的常规临床评估中可以合理选择患者进行靶向治疗临床试验，从而提高此类试验成功的可能性。
Gliomas consist of multiple histologic and molecular subtypes with different clinical phenotypes and responsiveness to treatment. However, enrollment criteria for clinical trials still largely do not take into account these underlying molecular differences. We have incorporated a high-throughput tumor genotyping program based on the ABI SNaPshot platform as well as other molecular diagnostic tests into the standard evaluation of glioma patients in order to assess whether prospective molecular profiling would allow rational patient selection onto clinical trials. From 218 gliomas we prospectively collected SNaPshot genotyping data on 68 mutated loci from 15 key cancer genes along with data from clinical assays for gene amplification (EGFR, PDGFRA, MET), 1p/19q co-deletion and MGMT promoter methylation. SNaPshot mutations and focal gene amplifications were detected in 38.5 and 47.1 % of glioblastomas, respectively. Genetic alterations in EGFR, IDH1 and PIK3CA closely matched frequencies reported in recent studies. In addition, we identified events that are rare in gliomas although are known driver mutations in other cancer types, such as mutations of AKT1, BRAF and KRAS. Patients with genetic alterations that activate signaling pathways were enrolled onto genetically selective clinical trials for malignant glioma as well as for other solid cancers. High-throughput molecular profiling incorporated into the routine clinical evaluation of glioma patients may enable the rational selection of patients for targeted therapy clinical trials and thereby improve the likelihood that such trials succeed.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
宇宙（癌症中的体细胞突变目录）数据库和网站。
影响因子：
8.8
作者：
Bamford, S;Dawson, E;Forbes, S;Clements, J;Pettett, R;Dogan, A;Flanagan, A;Teague, J;Futreal, PA;Stratton, MR;Wooster, R
通讯作者：
Wooster, R
影响因子：
48
作者：
Jansen, Michael;Yip, Stephen;Louis, David N.
通讯作者：
Louis, David N.
有效使用 PI3K 和 MEK 抑制剂治疗突变型 Kras G12D 和 PIK3CA H1047R 小鼠肺癌。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
45.3
作者：
Sanson, Marc;Marie, Yannick;Delattre, Jean-Yves
通讯作者：
Delattre, Jean-Yves