The mutational landscape of chromatin regulatory factors across 4,623 tumor samples.
The mutational landscape of chromatin regulatory factors across 4,623 tumor samples.
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DOI：
10.1186/gb-2013-14-9-r106
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发表时间：
2013
期刊：
影响因子：
12.3
通讯作者：
Lopez-Bigas N
中科院分区：
文献类型：
--
作者：
Gonzalez-Perez A;Jene-Sanz A;Lopez-Bigas N
染色质调节因子是癌症发生发展中的重要基因，被认为是癌症治疗新靶点的有趣候选者。然而，我们对这组基因在不同癌症类型中的作用缺乏全面的了解。我们分析了来自13个解剖部位的4，623个肿瘤样本，以确定哪些染色质调节因子是这些不同部位的候选驱动因子。我们确定了34个染色质调节因子，它们可能是来自至少一个位点的肿瘤驱动因子，所有这些因子的突变频率都相对较低。我们还分析了这组基因突变对每个位点肿瘤发生发展的相对重要性，以及同一位点不同肿瘤类型的相对重要性。我们发现，尽管来自所有13个位点的肿瘤在可能的驱动染色质调节因子中显示出突变，但这些突变在某些组织产生的肿瘤中更普遍。除了造血、肝脏和肾脏肿瘤之外，作为中位数，突变因子在所分析的所有位点中少于所有突变驱动因子的五分之一。我们还表明，在这些基因中的两个，MLL和EP300，突变与广泛的表达变化在癌细胞系，从而提出了至少一种机制，通过这些突变可能有助于在相应组织的细胞中的肿瘤发生。
Chromatin regulatory factors are emerging as important genes in cancer development and are regarded as interesting candidates for novel targets for cancer treatment. However, we lack a comprehensive understanding of the role of this group of genes in different cancer types. We have analyzed 4,623 tumor samples from thirteen anatomical sites to determine which chromatin regulatory factors are candidate drivers in these different sites. We identify 34 chromatin regulatory factors that are likely drivers in tumors from at least one site, all with relatively low mutational frequency. We also analyze the relative importance of mutations in this group of genes for the development of tumorigenesis in each site, and in different tumor types from the same site. We find that, although tumors from all thirteen sites show mutations in likely driver chromatin regulatory factors, these are more prevalent in tumors arising from certain tissues. With the exception of hematopoietic, liver and kidney tumors, as a median, the mutated factors are less than one fifth of all mutated drivers across all sites analyzed. We also show that mutations in two of these genes, MLL and EP300, correlate with broad expression changes across cancer cell lines, thus presenting at least one mechanism through which these mutations could contribute to tumorigenesis in cells of the corresponding tissues.
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影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
影响因子：
11.2
作者：
Banine, F;Bartlett, C;Sherman, LS
通讯作者：
Sherman, LS
影响因子：
3.7
作者：
Domenech, Elena;Gomez-Lopez, Gonzalo;Sanchez-Beato, Margarita
通讯作者：
Sanchez-Beato, Margarita
影响因子：
64.8
作者：
Biankin, Andrew V.;Waddell, Nicola;Kassahn, Karin S.;Gingras, Marie-Claude;Muthuswamy, Lakshmi B.;Johns, Amber L.;Miller, David K.;Wilson, Peter J.;Patch, Ann-Marie;Wu, Jianmin;Chang, David K.;Cowley, Mark J.;Gardiner, Brooke B.;Song, Sarah;Harliwong, Ivon;Idrisoglu, Senel;Nourse, Craig;Nourbakhsh, Ehsan;Manning, Suzanne;Wani, Shivangi;Gongora, Milena;Pajic, Marina;Scarlett, Christopher J.;Gill, Anthony J.;Pinho, Andreia V.;Rooman, Ilse;Anderson, Matthew;Holmes, Oliver;Leonard, Conrad;Taylor, Darrin;Wood, Scott;Xu, Qinying;Nones, Katia;Fink, J. Lynn;Christ, Angelika;Bruxner, Tim;Cloonan, Nicole;Kolle, Gabriel;Newell, Felicity;Pinese, Mark;Mead, R. Scott;Humphris, Jeremy L.;Kaplan, Warren;Jones, Marc D.;Colvin, Emily K.;Nagrial, Adnan M.;Humphrey, Emily S.;Chou, Angela;Chin, Venessa T.;Chantrill, Lorraine A.;Mawson, Amanda;Samra, Jaswinder S.;Kench, James G.;Lovell, Jessica A.;Daly, Roger J.;Merrett, Neil D.;Toon, Christopher;Epari, Krishna;Nguyen, Nam Q.;Barbour, Andrew;Zeps, Nikolajs;Kakkar, Nipun;Zhao, Fengmei;Wu, Yuan Qing;Wang, Min;Muzny, Donna M.;Fisher, William E.;Brunicardi, F. Charles;Hodges, Sally E.;Reid, Jeffrey G.;Drummond, Jennifer;Chang, Kyle;Han, Yi;Lewis, Lora R.;Dinh, Huyen;Buhay, Christian J.;Beck, Timothy;Timms, Lee;Sam, Michelle;Begley, Kimberly;Brown, Andrew;Pai, Deepa;Panchal, Ami;Buchner, Nicholas;De Borja, Richard;Denroche, Robert E.;Yung, Christina K.;Serra, Stefano;Onetto, Nicole;Mukhopadhyay, Debabrata;Tsao, Ming-Sound;Shaw, Patricia A.;Petersen, Gloria M.;Gallinger, Steven;Hruban, Ralph H.;Maitra, Anirban;Iacobuzio-Donahue, Christine A.;Schulick, Richard D.;Wolfgang, Christopher L.;Morgan, Richard A.;Lawlor, Rita T.;Capelli, Paola;Corbo, Vincenzo;Scardoni, Maria;Tortora, Giampaolo;Tempero, Margaret A.;Mann, Karen M.;Jenkins, Nancy A.;Perez-Mancera, Pedro A.;Adams, David J.;Largaespada, David A.;Wessels, Lodewyk F. A.;Rust, Alistair G.;Stein, Lincoln D.;Tuveson, David A.;Copeland, Neal G.;Musgrove, Elizabeth A.;Scarpa, Aldo;Eshleman, James R.;Hudson, Thomas J.;Sutherland, Robert L.;Wheeler, David A.;Pearson, John V.;McPherson, John D.;Gibbs, Richard A.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.
影响因子：
3.8
作者：
Al Sarakbi W;Sasi W;Jiang WG;Roberts T;Newbold RF;Mokbel K
通讯作者：
Mokbel K