Detectable clonal mosaicism and its relationship to aging and cancer.
Detectable clonal mosaicism and its relationship to aging and cancer.
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DOI：
10.1038/ng.2270
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发表时间：
2012-05-06
期刊：
影响因子：
30.8
通讯作者：
Chanock, Stephen J.
中科院分区：
文献类型：
--
作者：
Jacobs, Kevin B.;Yeager, Meredith;Zhou, Weiyin;Wacholder, Sholom;Wang, Zhaoming;Rodriguez-Santiago, Benjamin;Hutchinson, Amy;Deng, Xiang;Liu, Chenwei;Horner, Marie-Josephe;Cullen, Michael;Epstein, Caroline G.;Burdett, Laurie;Dean, Michael C.;Chatterjee, Nilanjan;Sampson, Joshua;Chung, Charles C.;Kovaks, Joseph;Gapstur, Susan M.;Stevens, Victoria L.;Teras, Lauren T.;Gaudet, Mia M.;Albanes, Demetrius;Weinstein, Stephanie J.;Virtamo, Jarmo;Taylor, Philip R.;Freedman, Neal D.;Abnet, Christian C.;Goldstein, Alisa M.;Hu, Nan;Yu, Kai;Yuan, Jian-Min;Liao, Linda;Ding, Ti;Qiao, You-Lin;Gao, Yu-Tang;Koh, Woon-Puay;Xiang, Yong-Bing;Tang, Ze-Zhong;Fan, Jin-Hu;Aldrich, Melinda C.;Amos, Christopher;Blot, William J.;Bock, Cathryn H.;Gillanders, Elizabeth M.;Harris, Curtis C.;Haiman, Christopher A.;Henderson, Brian E.;Kolonel, Laurence N.;Le Marchand, Loic;McNeill, Lorna H.;Rybicki, Benjamin A.;Schwartz, Ann G.;Signorello, Lisa B.;Spitz, Margaret R.;Wiencke, John K.;Wrensch, Margaret;Wu, Xifeng;Zanetti, Krista A.;Ziegler, Regina G.;Figueroa, Jonine D.;Garcia-Closas, Montserrat;Malats, Nuria;Marenne, Gaelle;Prokunina-Olsson, Ludmila;Baris, Dalsu;Schwenn, Molly;Johnson, Alison;Landi, Maria Teresa;Goldin, Lynn;Consonni, Dario;Bertazzi, Pier Alberto;Rotunno, Melissa;Rajaraman, Preetha;Andersson, Ulrika;Freeman, Laura E. Beane;Berg, Christine D.;Buring, Julie E.;Butler, Mary A.;Carreon, Tania;Feychting, Maria;Ahlbom, Anders;Gaziano, J. Michael;Giles, Graham G.;Hallmans, Goran;Hankinson, Susan E.;Hartge, Patricia;Henriksson, Roger;Inskip, Peter D.;Johansen, Christoffer;Landgren, Annelie;McKean-Cowdin, Roberta;Michaud, Dominique S.;Melin, Beatrice S.;Peters, Ulrike;Ruder, Avima M.;Sesso, Howard D.;Severi, Gianluca;Shu, Xiao-Ou;Visvanathan, Kala;White, Emily;Wolk, Alicja;Zeleniuch-Jacquotte, Anne;Zheng, Wei;Silverman, Debra T.;Kogevinas, Manolis;Gonzalez, Juan R.;Villa, Olaya;Li, Donghui;Duell, Eric J.;Risch, Harvey A.;Olson, Sara H.;Kooperberg, Charles;Wolpin, Brian M.;Jiao, Li;Hassan, Manal;Wheeler, William;Arslan, Alan A.;Bueno-de-Mesquita, H. Bas;Fuchs, Charles S.;Gallinger, Steven;Gross, Myron D.;Holly, Elizabeth A.;Klein, Alison P.;LaCroix, Andrea;Mandelson, Margaret T.;Petersen, Gloria;Boutron-Ruault, Marie-Christine;Bracci, Paige M.;Canzian, Federico;Chang, Kenneth;Cotterchio, Michelle;Giovannucci, Edward L.;Goggins, Michael;Bolton, Judith A. Hoffman;Jenab, Mazda;Khaw, Kay-Tee;Krogh, Vittorio;Kurtz, Robert C.;McWilliams, Robert R.;Mendelsohn, Julie B.;Rabe, Kari G.;Riboli, Elio;Tjonneland, Anne;Tobias, Geoffrey S.;Trichopoulos, Dimitrios;Elena, Joanne W.;Yu, Herbert;Amundadottir, Laufey;Stolzenberg-Solomon, Rachael Z.;Kraft, Peter;Schumacher, Fredrick;Stram, Daniel;Savage, Sharon A.;Mirabello, Lisa;Andrulis, Irene L.;Wunder, Jay S.;Patino Garcia, Ana;Sierrasesumaga, Luis;Barkauskas, Donald A.;Gorlick, Richard G.;Purdue, Mark;Chow, Wong-Ho;Moore, Lee E.;Schwartz, Kendra L.;Davis, Faith G.;Hsing, Ann W.;Berndt, Sonja I.;Black, Amanda;Wentzensen, Nicolas;Brinton, Louise A.;Lissowska, Jolanta;Peplonska, Beata;McGlynn, Katherine A.;Cook, Michael B.;Graubard, Barry I.;Kratz, Christian P.;Greene, Mark H.;Erickson, Ralph L.;Hunter, David J.;Thomas, Gilles;Hoover, Robert N.;Real, Francisco X.;Fraumeni, Joseph F., Jr.;Caporaso, Neil E.;Tucker, Margaret;Rothman, Nathaniel;Perez-Jurado, Luis A.;Chanock, Stephen J.
在对来自13项全基因组关联研究（GWAS）的31，717例癌症病例和26，136例无癌症对照的分析中，我们在从血液或口腔样本中获得的DNA的克隆子集中观察到了大的染色体异常。在517个个体（0.89%）的常染色体中观察到大小>2 Mb的嵌合染色体异常，非整倍体或拷贝中性杂合性丢失，异常细胞比例在7%和95%之间。在无癌个体中，频率随年龄增加而增加; 50岁以下为0.23%，75岁至79岁为1.91%（p=4.8×10−8）。镶嵌异常在实体瘤患者中更常见（0.97% vs 0.74%，无癌症患者，OR=1.25，p=0.016），与诊断或治疗前收集DNA的病例相关性更强（OR=1.45，p=0.0005）。与无癌症个体相比，在白血病诊断前至少一年收集DNA的个体中，可检测的克隆嵌合现象很常见（OR=35.4，p=3.8×10−11）。这些发现强调了癌症和其他迟发性疾病病因学中躯体事件的作用和时间依赖性的重要性。
In an analysis of 31,717 cancer cases and 26,136 cancer-free controls drawn from 13 genome-wide association studies (GWAS), we observed large chromosomal abnormalities in a subset of clones from DNA obtained from blood or buccal samples. Mosaic chromosomal abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of size >2 Mb were observed in autosomes of 517 individuals (0.89%) with abnormal cell proportions between 7% and 95%. In cancer-free individuals, the frequency increased with age; 0.23% under 50 and 1.91% between 75 and 79 (p=4.8×10−8). Mosaic abnormalities were more frequent in individuals with solid-tumors (0.97% versus 0.74% in cancer-free individuals, OR=1.25, p=0.016), with a stronger association for cases who had DNA collected prior to diagnosis or treatment (OR=1.45, p=0.0005). Detectable clonal mosaicism was common in individuals for whom DNA was collected at least one year prior to diagnosis of leukemia compared to cancer-free individuals (OR=35.4, p=3.8×10−11). These findings underscore the importance of the role and time-dependent nature of somatic events in the etiology of cancer and other late-onset diseases.
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影响因子：
64.8
作者：
通讯作者：
--
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：
30.8
作者：
Laurie, Cathy C.;Laurie, Cecelia A.;Rice, Kenneth;Doheny, Kimberly F.;Zelnick, Leila R.;McHugh, Caitlin P.;Ling, Hua;Hetrick, Kurt N.;Pugh, Elizabeth W.;Amos, Chris;Wei, Qingyi;Wang, Li-E;Lee, Jeffrey E.;Barnes, Kathleen C.;Hansel, Nadia N.;Mathias, Rasika;Daley, Denise;Beaty, Terri H.;Scott, Alan F.;Ruczinski, Ingo;Scharpf, Rob B.;Bierut, Laura J.;Hartz, Sarah M.;Landi, Maria Teresa;Freedman, Neal D.;Goldin, Lynn R.;Ginsburg, David;Li, Jun;Desch, Karl C.;Strom, Sara S.;Blot, William J.;Signorello, Lisa B.;Ingles, Sue A.;Chanock, Stephen J.;Berndt, Sonja I.;Le Marchand, Loic;Henderson, Brian E.;Monroe, Kristine R.;Heit, John A.;de Andrade, Mariza;Armasu, Sebastian M.;Regnier, Cynthia;Lowe, William L.;Hayes, M. Geoffrey;Marazita, Mary L.;Feingold, Eleanor;Murray, Jeffrey C.;Melbye, Mads;Feenstra, Bjarke;Kang, Jae H.;Wiggs, Janey L.;Jarvik, Gail P.;McDavid, Andrew N.;Seshan, Venkatraman E.;Mirel, Daniel B.;Crenshaw, Andrew;Sharopova, Nataliya;Wise, Anastasia;Shen, Jess;Crosslin, David R.;Levine, David M.;Zheng, Xiuwen;Udren, Jenna I.;Bennett, Siiri;Nelson, Sarah C.;Gogarten, Stephanie M.;Conomos, Matthew P.;Heagerty, Patrick;Manolio, Teri;Pasquale, Louis R.;Haiman, Christopher A.;Caporaso, Neil;Weir, Bruce S.
通讯作者：
Weir, Bruce S.
影响因子：
4
作者：
Menten, B.;Maas, N.;Vermeesch, J. R.
通讯作者：
Vermeesch, J. R.
影响因子：
1.8
作者：
Agresti, A;Coull, BA
通讯作者：
Coull, BA