Cancer driver mutations in protein kinase genes.
Cancer driver mutations in protein kinase genes.
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DOI：
10.1016/j.canlet.2008.11.008
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发表时间：
2009-08-28
期刊：
影响因子：
9.7
通讯作者：
Schork, Nicholas J.
中科院分区：
文献类型：
--
作者：
Torkamani, Ali;Verkhivker, Gennady;Schork, Nicholas J.
最近研究癌症的遗传决定因素的研究表明，一些有助于肿瘤发生的遗传改变可能是遗传的，但绝大多数是在正常细胞向癌细胞转变期间获得的。对癌症的遗传和分子决定因素的系统了解已经开始对癌症的研究和治疗产生变革性影响，特别是通过鉴定与疾病高度相关的蛋白激酶基因中的一系列遗传改变。由于激酶是癌细胞内干预的重要治疗靶点，因此研究它们内部的基因组改变对癌症发生、进展和治疗的影响既合乎逻辑又及时。事实上，最近的测序和重测序（即，多态性鉴定）的努力已经催化了对蛋白激酶“驱动”突变的探索（即，那些有助于正常细胞转化为增殖癌细胞的遗传改变）与激酶“过客”突变不同，激酶“过客”突变反映了仅在正常和未受抑制的过程中积累的突变（即，癌）体细胞复制和增殖。在这篇综述中，我们讨论了蛋白激酶癌症驱动突变的发现和功能表征的最新进展，以及这一进展对理解肿瘤发生的影响，以及针对个体独特突变特征的“个性化”癌症治疗方法的设计。
Recent studies investigating the genetic determinants of cancer suggest that some of the genetic alterations contributing to tumorigenesis may be inherited, but the vast majority are somatically acquired during the transition of a normal cell to a cancer cell. A systematic understanding of the genetic and molecular determinants of cancers has already begun to have a transformative effect on the study and treatment of cancer, particularly through the identification of a range of genetic alterations in protein kinase genes, which are highly associated with the disease. Since kinases are prominent therapeutic targets for intervention within the cancer cell, studying the impact that genomic alterations within them have on cancer initiation, progression, and treatment is both logical and timely. In fact, recent sequencing and resequencing (i.e., polymorphism idenitification) efforts have catalyzed the quest for protein kinase ‘driver’ mutations (i.e., those genetic alterations which contribute to the transformation of a normal cell to a proliferating cancerous cell) in distinction to kinase ‘passenger’ mutations which reflect mutations that merely build up in course of normal and unchecked (i.e., cancerous) somatic cell replication and proliferation. In this review, we discuss the recent progress in the discovery and functional characterization of protein kinase cancer driver mutations and the implications of this progress for understanding tumorigenesis as well as the design of ‘personalized’ cancer therapeutics that target an individual’s unique mutational profile.
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
4.3
作者：
Dussault, Isabelle;Bellon, Steven F.
通讯作者：
Bellon, Steven F.
影响因子：
11.2
作者：
Engelman, Jeffrey A.;Zejnullahu, Kreshnik;Janne, Pasi A.
通讯作者：
Janne, Pasi A.
影响因子：
11.2
作者：
Cranston, Aaron N.;Carniti, Cristiana;Ponder, Bruce A. J.
通讯作者：
Ponder, Bruce A. J.
影响因子：
8
作者：
Chen, Z.;Feng, J.;Sommer, S. S.
通讯作者：
Sommer, S. S.