High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.
High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.
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DOI：
10.1038/nbt.3460
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发表时间：
2016-04
影响因子：
46.9
通讯作者：
Golub TR
中科院分区：
文献类型：
--
作者：
Yu C;Mannan AM;Yvone GM;Ross KN;Zhang YL;Marton MA;Taylor BR;Crenshaw A;Gould JZ;Tamayo P;Weir BA;Tsherniak A;Wong B;Garraway LA;Shamji AF;Palmer MA;Foley MA;Winckler W;Schreiber SL;Kung AL;Golub TR
数百种具有基因特征的细胞系可用于发现特定于基因的癌症易损性。然而，目前针对大量细胞系筛选大量化合物是不切实际的，而且这样的实验往往很难控制。在这里，我们报告了一种名为PRISM的方法，它允许通过用24个核苷酸条形码标记每个细胞系来共同筛选癌细胞系的混合物。棱镜显示了在常规(未合并)分析中看到的预期的细胞杀伤模式。在对8,400种化合物的102个细胞株的筛选中，PRISM导致BRD-7880被鉴定为一种有效的和高度特异的极光蛋白激酶B和C的抑制剂。
Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here, we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM displayed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo.
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影响因子：
64.5
作者：
Basu A;Bodycombe NE;Cheah JH;Price EV;Liu K;Schaefer GI;Ebright RY;Stewart ML;Ito D;Wang S;Bracha AL;Liefeld T;Wawer M;Gilbert JC;Wilson AJ;Stransky N;Kryukov GV;Dancik V;Barretina J;Garraway LA;Hon CS;Munoz B;Bittker JA;Stockwell BR;Khabele D;Stern AM;Clemons PA;Shamji AF;Schreiber SL
通讯作者：
Schreiber SL
影响因子：
12.3
作者：
Peck, David;D Crawford, Emily;Ross, Kenneth N.;Stegmaier, Kimberly;Golub, Todd R.;Lamb, Justin
通讯作者：
Lamb, Justin
影响因子：
15
作者：
Marcaurelle, Lisa A.;Comer, Eamon;Dandapani, Sivaraman;Duvall, Jeremy R.;Gerard, Baudouin;Kesavan, Sarathy;Lee, Maurice D.;Liu, Haibo;Lowe, Jason T.;Marie, Jean-Charles;Mulrooney, Carol A.;Pandya, Bhaumik A.;Rowley, Ann;Ryba, Troy D.;Suh, Byung-Chul;Wei, Jingqiang;Young, Damian W.;Akella, Lakshmi B.;Ross, Nathan T.;Zhang, Yan-Ling;Fass, Daniel M.;Reis, Surya A.;Zhao, Wen-Ning;Haggarty, Stephen J.;Palmer, Michelle;Foley, Michael A.
通讯作者：
Foley, Michael A.
影响因子：
64.8
作者：
Garnett, Mathew J.;Edelman, Elena J.;Heidorn, Sonja J.;Greenman, Chris D.;Dastur, Anahita;Lau, King Wai;Greninger, Patricia;Thompson, I. Richard;Luo, Xi;Soares, Jorge;Liu, Qingsong;Iorio, Francesco;Surdez, Didier;Chen, Li;Milano, Randy J.;Bignell, Graham R.;Tam, Ah T.;Davies, Helen;Stevenson, Jesse A.;Barthorpe, Syd;Lutz, Stephen R.;Kogera, Fiona;Lawrence, Karl;McLaren-Douglas, Anne;Mitropoulos, Xeni;Mironenko, Tatiana;Thi, Helen;Richardson, Laura;Zhou, Wenjun;Jewitt, Frances;Zhang, Tinghu;O'Brien, Patrick;Boisvert, Jessica L.;Price, Stacey;Hur, Wooyoung;Yang, Wanjuan;Deng, Xianming;Butler, Adam;Choi, Hwan Geun;Chang, JaeWon;Baselga, Jose;Stamenkovic, Ivan;Engelman, Jeffrey A.;Sharma, Sreenath V.;Delattre, Olivier;Saez-Rodriguez, Julio;Gray, Nathanael S.;Settleman, Jeffrey;Futreal, P. Andrew;Haber, Daniel A.;Stratton, Michael R.;Ramaswamy, Sridhar;McDermott, Ultan;Benes, Cyril H.
通讯作者：
Benes, Cyril H.
影响因子：
46.9
作者：
Du, Jinyan;Bernasconi, Paula;Clauser, Karl R.;Mani, D. R.;Finn, Stephen P.;Beroukhim, Rameen;Burns, Melissa;Julian, Bina;Peng, Xiao P.;Hieronymus, Haley;Maglathlin, Rebecca L.;Lewis, Timothy A.;Liau, Linda M.;Nghiemphu, Phioanh;Mellinghoff, Ingo K.;Louis, David N.;Loda, Massimo;Carr, Steven A.;Kung, Andrew L.;Golub, Todd R.
通讯作者：
Golub, Todd R.