Unique features of the transcriptional response to model aneuploidy in human cells.
Unique features of the transcriptional response to model aneuploidy in human cells.
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DOI：
10.1186/1471-2164-15-139
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发表时间：
2014-02-18
期刊：
影响因子：
4.4
通讯作者：
Storchová Z
中科院分区：
文献类型：
--
作者：
Dürrbaum M;Kuznetsova AY;Passerini V;Stingele S;Stoehr G;Storchová Z
非整倍性是一种与多个单倍体染色体组不同的核型，它影响真核生物的生理功能。在人类中，非整倍体与病理缺陷有关，如发育异常，智力迟钝或癌症，但其潜在机制仍然难以捉摸。非整倍体有许多不同的类型和起源，但迄今为止，人类细胞中是否存在对非整倍体的统一细胞反应还没有得到解决。在这里，我们评估了11个三体和四体细胞系和两个细胞系复杂的非整倍体核型的转录谱。我们确定了一个特征性的非整倍体反应模式定义的内质网，高尔基体和溶酶体的基因上调，下调DNA复制，转录以及核糖体。引人注目的是，复杂的非整倍体引起了与三体性相同的转录变化。为了揭示这种反应的触发因素，我们将这些图谱与处于应激条件下的人类细胞中的转录变化进行了比较。有趣的是，我们发现仅与自噬抑制剂巴弗洛霉素A1治疗的反应重叠。最后，我们确定了23个基因的表达显着改变，在所有的非整倍体，因此可以作为非整倍体标记。我们的分析表明，尽管染色体内容的变异性，非整倍体触发人类细胞中的统一转录反应。一个共同的反应独立于非整倍体的类型可能会被开发作为一个新的癌症治疗的目标。此外，在我们的分析中确定的潜在的非整倍体标志物可能代表新的生物标志物，以评估肿瘤的恶性潜力。
Aneuploidy, a karyotype deviating from multiples of a haploid chromosome set, affects the physiology of eukaryotes. In humans, aneuploidy is linked to pathological defects such as developmental abnormalities, mental retardation or cancer, but the underlying mechanisms remain elusive. There are many different types and origins of aneuploidy, but whether there is a uniform cellular response to aneuploidy in human cells has not been addressed so far. Here we evaluate the transcription profiles of eleven trisomic and tetrasomic cell lines and two cell lines with complex aneuploid karyotypes. We identify a characteristic aneuploidy response pattern defined by upregulation of genes linked to endoplasmic reticulum, Golgi apparatus and lysosomes, and downregulation of DNA replication, transcription as well as ribosomes. Strikingly, complex aneuploidy elicits the same transcriptional changes as trisomy. To uncover the triggers of the response, we compared the profiles with transcription changes in human cells subjected to stress conditions. Interestingly, we found an overlap only with the response to treatment with the autophagy inhibitor bafilomycin A1. Finally, we identified 23 genes whose expression is significantly altered in all aneuploids and which may thus serve as aneuploidy markers. Our analysis shows that despite the variability in chromosome content, aneuploidy triggers uniform transcriptional response in human cells. A common response independent of the type of aneuploidy might be exploited as a novel target for cancer therapy. Moreover, the potential aneuploidy markers identified in our analysis might represent novel biomarkers to assess the malignant potential of a tumor.
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影响因子：
64.8
作者：
Burrell RA;McClelland SE;Endesfelder D;Groth P;Weller MC;Shaikh N;Domingo E;Kanu N;Dewhurst SM;Gronroos E;Chew SK;Rowan AJ;Schenk A;Sheffer M;Howell M;Kschischo M;Behrens A;Helleday T;Bartek J;Tomlinson IP;Swanton C
通讯作者：
Swanton C
影响因子：
6.4
作者：
Duijf, Pascal H. G.;Schultz, Nikolaus;Benezra, Robert
通讯作者：
Benezra, Robert
影响因子：
30.8
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.
通讯作者：
Chanock, Stephen J.
影响因子：
29.7
作者：
Blum JS;Wearsch PA;Cresswell P
通讯作者：
Cresswell P
影响因子：
10.5
作者：
Oromendia, Ana B.;Dodgson, Stacie E.;Amon, Angelika
通讯作者：
Amon, Angelika