Comprehensive molecular characterization of human colon and rectal cancer.
Comprehensive molecular characterization of human colon and rectal cancer.
复制标题
DOI：
10.1038/nature11252
复制
发表时间：
2012-07-18
期刊：
影响因子：
64.8
通讯作者：
Thomson, Elizabeth
中科院分区：
文献类型：
--
作者：
Muzny, Donna M.;Bainbridge, Matthew N.;Chang, Kyle;Dinh, Huyen H.;Drummond, Jennifer A.;Fowler, Gerald;Kovar, Christie L.;Lewis, Lora R.;Morgan, Margaret B.;Newsham, Irene F.;Reid, Jeffrey G.;Santibanez, Jireh;Shinbrot, Eve;Trevino, Lisa R.;Wu, Yuan-Qing;Wang, Min;Gunaratne, Preethi;Donehower, Lawrence A.;Creighton, Chad J.;Wheeler, David A.;Gibbs, Richard A.;Lawrence, Michael S.;Voet, Douglas;Jing, Rui;Cibulskis, Kristian;Sivachenko, Andrey;Stojanov, Petar;McKenna, Aaron;Lander, Eric S.;Gabriel, Stacey;Getz, Gad;Ding, Li;Fulton, Robert S.;Koboldt, Daniel C.;Wylie, Todd;Walker, Jason;Dooling, David J.;Fulton, Lucinda;Delehaunty, Kim D.;Fronick, Catrina C.;Demeter, Ryan;Mardis, Elaine R.;Wilson, Richard K.;Chu, Andy;Chun, Hye-Jung E.;Mungall, Andrew J.;Pleasance, Erin;Robertson, A. Gordon;Stoll, Dominik;Balasundaram, Miruna;Birol, Inanc;Butterfield, Yaron S. N.;Chuah, Eric;Coope, Robin J. N.;Dhalla, Noreen;Guin, Ranabir;Hirst, Carrie;Hirst, Martin;Holt, Robert A.;Lee, Darlene;Li, Haiyan I.;Mayo, Michael;Moore, Richard A.;Schein, Jacqueline E.;Slobodan, Jared R.;Tam, Angela;Thiessen, Nina;Varhol, Richard;Zeng, Thomas;Zhao, Yongjun;Jones, Steven J. M.;Marra, Marco A.;Bass, Adam J.;Ramos, Alex H.;Saksena, Gordon;Cherniack, Andrew D.;Schumacher, Stephen E.;Tabak, Barbara;Carter, Scott L.;Pho, Nam H.;Nguyen, Huy;Onofrio, Robert C.;Crenshaw, Andrew;Ardlie, Kristin;Beroukhim, Rameen;Winckler, Wendy;Getz, Gad;Meyerson, Matthew;Protopopov, Alexei;Zhang, Juinhua;Hadjipanayis, Angela;Lee, Eunjung;Xi, Ruibin;Yang, Lixing;Ren, Xiaojia;Zhang, Hailei;Sathiamoorthy, Narayanan;Shukla, Sachet;Chen, Peng-Chieh;Haseley, Psalm;Xiao, Yonghong;Lee, Semin;Seidman, Jonathan;Chin, Lynda;Park, Peter J.;Kucherlapati, Raju;Auman, J. Todd;Hoadley, Katherine A.;Du, Ying;Wilkerson, Matthew D.;Shi, Yan;Liquori, Christina;Meng, Shaowu;Li, Ling;Turman, Yidi J.;Topal, Michael D.;Tan, Donghui;Waring, Scot;Buda, Elizabeth;Walsh, Jesse;Jones, Corbin D.;Mieczkowski, Piotr A.;Singh, Darshan;Wu, Junyuan;Gulabani, Anisha;Dolina, Peter;Bodenheimer, Tom;Hoyle, Alan P.;Simons, Janae V.;Soloway, Matthew;Mose, Lisle E.;Jefferys, Stuart R.;Balu, Saianand;O'Connor, Brian D.;Prins, Jan F.;Chiang, Derek Y.;Hayes, D. Neil;Perou, Charles M.;Hinoue, Toshinori;Weisenberger, Daniel J.;Maglinte, Dennis T.;Pan, Fei;Berman, Benjamin P.;Van den Berg, David J.;Shen, Hui;Triche, Timothy, Jr.;Baylin, Stephen B.;Laird, Peter W.;Getz, Gad;Noble, Michael;Voet, Doug;Saksena, Gordon;Gehlenborg, Nils;DiCara, Daniel;Zhang, Juinhua;Zhang, Hailei;Wu, Chang-Jiun;Liu, Spring Yingchun;Shukla, Sachet;Lawrence, Michael S.;Zhou, Lihua;Sivachenko, Andrey;Lin, Pei;Stojanov, Petar;Jing, Rui;Park, Richard W.;Nazaire, Marc-Danie;Robinson, Jim;Thorvaldsdottir, Helga;Mesirov, Jill;Park, Peter J.;Chin, Lynda;Thorsson, Vesteinn;Reynolds, Sheila M.;Bernard, Brady;Kreisberg, Richard;Lin, Jake;Iype, Lisa;Bressler, Ryan;Erkkilae, Timo;Gundapuneni, Madhumati;Liu, Yuexin;Norberg, Adam;Robinson, Tom;Da Yang;Zhang, Wei;Shmulevich, Ilya;De Ronde, Jorma J.;Schultz, Nikolaus;Cerami, Ethan;Ciriello, Giovanni;Goldberg, Arthur P.;Gross, Benjamin;Jacobsen, Anders;Gao, Jianjiong;Kaczkowski, Bogumil;Sinha, Rileen;Aksoy, B. Arman;Antipin, Yevgeniy;Reva, Boris;Shen, Ronglai;Taylor, Barry S.;Chan, Timothy A.;Ladanyi, Marc;Sander, Chris;Akbani, Rehan;Zhang, Nianxiang;Broom, Bradley M.;Casasent, Tod;Unruh, Anna;Wakefield, Chris;Hamilton, Stanley R.;Cason, R. Craig;Baggerly, Keith A.;Weinstein, John N.;Haussler, David;Benz, Christopher C.;Stuart, Joshua M.;Benz, Stephen C.;Sanborn, J. Zachary;Vaske, Charles J.;Zhu, Jingchun;Szeto, Christopher;Scott, Gary K.;Yau, Christina;Ng, Sam;Goldstein, Ted;Ellrott, Kyle;Collisson, Eric;Cozen, Aaron E.;Zerbino, Daniel;Wilks, Christopher;Craft, Brian;Spellman, Paul;Penny, Robert;Shelton, Troy;Hatfield, Martha;Morris, Scott;Yena, Peggy;Shelton, Candace;Sherman, Mark;Paulauskis, Joseph;Gastier-Foster, Julie M.;Bowen, Jay;Ramirez, Nilsa C.;Black, Aaron;Pyatt, Robert;Wise, Lisa;White, Peter;Bertagnolli, Monica;Brown, Jen;Chan, Timothy A.;Chu, Gerald C.;Czerwinski, Christine;Denstman, Fred;Dhir, Rajiv;Doerner, Arnulf;Fuchs, Charles S.;Guillem, Jose G.;Iacocca, Mary;Juhl, Hartmut;Kaufman, Andrew;Kohl, Bernard, III;Van Le, Xuan;Mariano, Maria C.;Medina, Elizabeth N.;Meyers, Michael;Nash, Garrett M.;Paty, Phillip B.;Petrelli, Nicholas;Rabeno, Brenda;Richards, William G.;Solit, David;Swanson, Pat;Temple, Larissa;Tepper, Joel E.;Thorp, Richard;Vakiani, Efsevia;Weiser, Martin R.;Willis, Joseph E.;Witkin, Gary;Zeng, Zhaoshi;Zinner, Michael J.;Zornig, Carsten;Jensen, Mark A.;Sfeir, Robert;Kahn, Ari B.;Chu, Anna L.;Kothiyal, Prachi;Wang, Zhining;Snyder, Eric E.;Pontius, Joan;Pihl, Todd D.;Ayala, Brenda;Backus, Mark;Walton, Jessica;Whitmore, Jon;Baboud, Julien;Berton, Dominique L.;Nicholls, Matthew C.;Srinivasan, Deepak;Raman, Rohini;Girshik, Stanley;Kigonya, Peter A.;Alonso, Shelley;Sanbhadti, Rashmi N.;Barletta, Sean P.;Greene, John M.;Pot, David A.;Shaw, Kenna R. Mills;Dillon, Laura A. L.;Buetow, Ken;Davidsen, Tanja;Demchok, John A.;Eley, Greg;Ferguson, Martin;Fielding, Peter;Schaefer, Carl;Sheth, Margi;Yang, Liming;Guyer, Mark S.;Ozenberger, Bradley A.;Palchik, Jacqueline D.;Peterson, Jane;Sofia, Heidi J.;Thomson, Elizabeth
为了描述结直肠癌的体细胞变化，我们对276个样本进行了基因组规模的分析，分析了外显子序列、DNA拷贝数、启动子甲基化和信使RNA以及microRNA的表达。这些样本的一个子集(97个)接受了低覆盖深度的全基因组测序。总体而言，16%的结直肠癌被发现过度突变：其中四分之三具有预期的高微卫星不稳定性，通常伴有高甲基化和MLH1沉默，四分之一具有体细胞错配修复基因和聚合酶ε(POL)突变。除去过度突变的癌症，结肠癌和直肠癌的基因组改变模式非常相似。24个基因发生显著突变，除了预期的APC、TP53、Smad4、PIK3CA和KRAS突变外，我们还发现ARID1A、SOX9和FAM123B经常发生突变。反复发生的拷贝数改变包括潜在的药物靶向的ERBB2扩增和新发现的IGF2扩增。反复发生的染色体易位包括NAV2和WNT途径成员TCF7L1的融合。综合分析提示侵袭性结直肠癌的新标记物和MYC引导的转录激活和抑制的重要作用。本文的在线版本(doi：10.1038/Nature11252)包含补充材料，授权用户可以使用。癌症基因组图谱联盟报告了他们对结直肠癌体细胞变化的全基因组特征；除了揭示了基因组变化的显著一致模式，有24个基因发生显著突变外，这项研究还确定了治疗干预的新靶点，并提出了MYC导向的转录激活和抑制的重要作用。本文的在线版本(doi：10.1038/Nature11252)包含补充材料，授权用户可以使用。癌症基因组图谱联盟报告了他们对结直肠癌体细胞变化的全基因组特征。结合外显子序列数据、DNA拷贝数、启动子甲基化、信使RNA和microRNA表达，以及低覆盖率全基因组测序，显示16%的癌组织存在高突变。在这些人中，四分之三具有预期的高度微卫星不稳定性，但其余的人具有体细胞错配修复基因突变。这些数据显示了一个非常一致的基因组改变模式，有24个基因发生了显著突变。除了识别侵袭性结直肠癌的新生物标记物外，这些数据还暗示了MYC指导的转录激活和抑制的重要作用。本文的在线版本(doi：10.1038/Nature11252)包含补充材料，授权用户可以使用。
To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ε (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. The online version of this article (doi:10.1038/nature11252) contains supplementary material, which is available to authorized users. The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression. The online version of this article (doi:10.1038/nature11252) contains supplementary material, which is available to authorized users. The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal carcinoma. Combined analysis of exome sequence data, DNA copy number, promoter methylation, messenger RNA and microRNA expression, as well as low-coverage whole-genome sequencing reveal that 16% of these carcinomas have hypermutation. Of these, three-quarters have the expected high microsatellite instability, but the rest have somatic mismatch repair gene mutations. The data reveal a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated. As well as identifying new biomarkers for aggressive colorectal carcinoma, the data imply an important role for MYC-directed transcriptional activation and repression. The online version of this article (doi:10.1038/nature11252) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
7
作者：
Hinoue, Toshinori;Weisenberger, Daniel J.;Laird, Peter W.
通讯作者：
Laird, Peter W.
DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
56.9
作者：
Cui, HM;Cruz-Correa, M;Feinberg, AP
通讯作者：
Feinberg, AP
DOI：
10.1002/gcc.20699
发表时间：
2009-11
期刊：
Genes, chromosomes & cancer
影响因子：
--
作者：
Camps J;Nguyen QT;Padilla-Nash HM;Knutsen T;McNeil NE;Wangsa D;Hummon AB;Grade M;Ried T;Difilippantonio MJ
通讯作者：
Difilippantonio MJ