Cancer vulnerabilities unveiled by genomic loss.
Cancer vulnerabilities unveiled by genomic loss.
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DOI：
10.1016/j.cell.2012.07.023
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发表时间：
2012-08-17
期刊：
影响因子：
64.5
通讯作者：
Hahn WC
中科院分区：
文献类型：
--
作者：
Nijhawan D;Zack TI;Ren Y;Strickland MR;Lamothe R;Schumacher SE;Tsherniak A;Besche HC;Rosenbluh J;Shehata S;Cowley GS;Weir BA;Goldberg AL;Mesirov JP;Root DE;Bhatia SN;Beroukhim R;Hahn WC
由于基因组不稳定，大多数癌症表现出含有肿瘤抑制基因的区域的丢失和其他基因的附带丢失。为了确定拷贝数缺失导致的癌症特异性脆弱性，我们对全基因组拷贝数和RNAi图谱进行了综合分析，并鉴定了56个基因，其中基因抑制特异性抑制了该基因部分拷贝数缺失的细胞的增殖。这些CYCLOPS（拷贝数改变导致癌症风险）基因富含剪接体、蛋白酶体和核糖体成分。其中一个CYCLOPS基因PSMC2编码s蛋白酶体的一个重要成员。正常细胞表达过量的PSMC2， PSMC2与PSMC1、PSMD2和PSMD5复合物存在，并作为储库保护细胞免受PSMC2抑制。PSMC2拷贝数部分缺失的细胞缺乏这种复合物，在PSMC2抑制后死亡。这些观察结果定义了由基因组不稳定性导致的一类独特的癌症特异性负债。
Due to genome instability, most cancers exhibit loss of regions containing tumor suppressor genes and collateral loss of other genes. To identify cancer-specific vulnerabilities that are the result of copy-number losses, we performed integrated analyses of genome-wide copy-number and RNAi profiles and identified 56 genes for which gene suppression specifically inhibited the proliferation of cells harboring partial copy-number loss of that gene. These CYCLOPS (Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS) genes are enriched for spliceosome, proteasome and ribosome components. One CYCLOPS gene, PSMC2, encodes an essential member of the 19S proteasome. Normal cells express excess PSMC2, which resides in a complex with PSMC1, PSMD2, and PSMD5 and acts as a reservoir protecting cells from PSMC2 suppression. Cells harboring partial PSMC2 copy-number loss lack this complex and die after PSMC2 suppression. These observations define a distinct class of cancer-specific liabilities resulting from genome instability.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
17.1
作者：
Ren Y;Cheung HW;von Maltzhan G;Agrawal A;Cowley GS;Weir BA;Boehm JS;Tamayo P;Karst AM;Liu JF;Hirsch MS;Mesirov JP;Drapkin R;Root DE;Lo J;Fogal V;Ruoslahti E;Hahn WC;Bhatia SN
通讯作者：
Bhatia SN
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.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
16.6
作者：
Finley D
通讯作者：
Finley D