Comprehensive molecular portraits of human breast tumours.
Comprehensive molecular portraits of human breast tumours.
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DOI：
10.1038/nature11412
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发表时间：
2012-10-04
期刊：
影响因子：
64.8
通讯作者：
Palchik, Jacqueline D.
中科院分区：
文献类型：
--
作者：
Koboldt, Daniel C.;Fulton, Robert S.;McLellan, Michael D.;Schmidt, Heather;Kalicki-Veizer, Joelle;McMichael, Joshua F.;Fulton, Lucinda L.;Dooling, David J.;Ding, Li;Mardis, Elaine R.;Wilson, Richard K.;Ally, Adrian;Balasundaram, Miruna;Butterfield, Yaron S. N.;Carlsen, Rebecca;Carter, Candace;Chu, Andy;Chuah, Eric;Chun, Hye-Jung E.;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.;Mungall, Andrew J.;Pleasance, Erin;Robertson, A. Gordon;Schein, Jacqueline E.;Shafiei, Arash;Sipahimalani, Payal;Slobodan, Jared R.;Stoll, Dominik;Tam, Angela;Thiessen, Nina;Varhol, Richard J.;Wye, Natasja;Zeng, Thomas;Zhao, Yongjun;Birol, Inanc;Jones, Steven J. M.;Marra, Marco A.;Cherniack, Andrew D.;Saksena, Gordon;Onofrio, Robert C.;Pho, Nam H.;Carter, Scott L.;Schumacher, Steven E.;Tabak, Barbara;Hernandez, Bryan;Gentry, Jeff;Huy Nguyen;Crenshaw, Andrew;Ardlie, Kristin;Beroukhim, Rameen;Winckler, Wendy;Getz, Gad;Gabriel, Stacey B.;Meyerson, Matthew;Chin, Lynda;Park, Peter J.;Kucherlapati, Raju;Hoadley, Katherine A.;Auman, J. Todd;Fan, Cheng;Turman, Yidi J.;Shi, Yan;Li, Ling;Topal, Michael D.;He, Xiaping;Chao, Hann-Hsiang;Prat, Aleix;Silva, Grace O.;Iglesia, Michael D.;Zhao, Wei;Usary, Jerry;Berg, Jonathan S.;Adams, Michael;Booker, Jessica;Wu, Junyuan;Gulabani, Anisha;Bodenheimer, Tom;Hoyle, Alan P.;Simons, Janae V.;Soloway, Matthew G.;Mose, Lisle E.;Jefferys, Stuart R.;Balu, Saianand;Parker, Joel S.;Hayes, D. Neil;Perou, Charles M.;Malik, Simeen;Mahurkar, Swapna;Shen, Hui;Weisenberger, Daniel J.;Triche, Timothy, Jr.;Lai, Phillip H.;Bootwalla, Moiz S.;Maglinte, Dennis T.;Berman, Benjamin P.;Van den Berg, David J.;Baylin, Stephen B.;Laird, Peter W.;Creighton, Chad J.;Donehower, Lawrence A.;Getz, Gad;Noble, Michael;Voet, Doug;Saksena, Gordon;Gehlenborg, Nils;DiCara, Daniel;Zhang, Juinhua;Zhang, Hailei;Wu, Chang-Jiun;Liu, Spring Yingchun;Lawrence, Michael S.;Zou, Lihua;Sivachenko, Andrey;Lin, Pei;Stojanov, Petar;Jing, Rui;Cho, Juok;Sinha, Raktim;Park, Richard W.;Nazaire, Marc-Danie;Robinson, Jim;Thorvaldsdottir, Helga;Mesirov, Jill;Park, Peter J.;Chin, Lynda;Reynolds, Sheila;Kreisberg, Richard B.;Bernard, Brady;Bressler, Ryan;Erkkila, Timo;Lin, Jake;Thorsson, Vesteinn;Zhang, Wei;Shmulevich, Ilya;Ciriello, Giovanni;Weinhold, Nils;Schultz, Nikolaus;Gao, Jianjiong;Cerami, Ethan;Gross, Benjamin;Jacobsen, Anders;Sinha, Rileen;Aksoy, B. Arman;Antipin, Yevgeniy;Reva, Boris;Shen, Ronglai;Taylor, Barry S.;Ladanyi, Marc;Sander, Chris;Anur, Pavana;Spellman, Paul T.;Lu, Yiling;Liu, Wenbin;Verhaak, Roel R. G.;Mills, Gordon B.;Akbani, Rehan;Zhang, Nianxiang;Broom, Bradley M.;Casasent, Tod D.;Wakefield, Chris;Unruh, Anna K.;Baggerly, Keith;Coombes, Kevin;Weinstein, John N.;Haussler, David;Benz, Christopher C.;Stuart, Joshua M.;Benz, Stephen C.;Zhu, Jingchun;Szeto, Christopher C.;Scott, Gary K.;Yau, Christina;Paul, Evan O.;Carlin, Daniel;Wong, Christopher;Sokolov, Artem;Thusberg, Janita;Mooney, Sean;Sam Ng;Goldstein, Theodore C.;Ellrott, Kyle;Grifford, Mia;Wilks, Christopher;Ma, Singer;Craft, Brian;Yan, Chunhua;Hu, Ying;Meerzaman, Daoud;Gastier-Foster, Julie M.;Bowen, Jay;Ramirez, Nilsa C.;Black, Aaron D.;Pyatt, Robert E.;White, Peter;Zmuda, Erik J.;Frick, Jessica;Lichtenberg, Taram.;Brookens, Robin;George, Myra M.;Gerken, Mark A.;Harper, Hollie A.;Leraas, Kristen M.;Wise, Lisa J.;Tabler, Teresa R.;McAllister, Cynthia;Barr, Thomas;Hart-Kothari, Melissa;Tarvin, Katie;Saller, Charles;Sandusky, George;Mitchell, Colleen;Iacocca, Mary V.;Brown, Jennifer;Rabeno, Brenda;Czerwinski, Christine;Petrelli, Nicholas;Dolzhansky, Oleg;Abramov, Mikhail;Voronina, Olga;Potapova, Olga;Marks, Jeffrey R.;Suchorska, Wiktoria M.;Murawa, Dawid;Kycler, Witold;Ibbs, Matthew;Korski, Konstanty;Spychala, Arkadiusz;Murawa, Pawel;Brzezinski, Jacek J.;Perz, Hanna;Lazniak, Radoslaw;Teresiak, Marek;Tatka, Honorata;Leporowska, Ewa;Bogusz-Czerniewicz, Marta;Malicki, Julian;Mackiewicz, Andrzej;Wiznerowicz, Maciej;Xuan Van Le;Kohl, Bernard;Nguyen Viet Tien;Thorp, Richard;Nguyen Van Bang;Sussman, Howard;Bui Duc Phu;Hajek, Richard;Nguyen Phi Hung;Tran Viet The Phuong;Huynh Quyet Thang;Khan, Khurram Zaki;Penny, Robert;Mallery, David;Curley, Erin;Shelton, Candace;Yena, Peggy;Ingle, James N.;Couch, Fergus J.;Lingle, Wilma L.;King, Tari A.;Gonzalez-Angulo, Ana Maria;Mills, Gordon B.;Dyer, Mary D.;Liu, Shuying;Meng, Xiaolong;Patangan, Modesto;Waldman, Frederic;Stoeppler, Hubert;Rathmell, W. Kimryn;Thorne, Leigh;Huang, Mei;Boice, Lori;Hill, Ashley;Morrison, Carl;Gaudioso, Carmelo;Bshara, Wiam;Daily, Kelly;Egea, Sophie C.;Pegram, Mark D.;Gomez-Fernandez, Carmen;Dhir, Rajiv;Bhargava, Rohit;Brufsky, Adam;Shriver, Craig D.;Hooke, Jeffrey A.;Campbell, Jamie Leigh;Mural, Richard J.;Hu, Hai;Somiari, Stella;Larson, Caroline;Deyarmin, Brenda;Kvecher, Leonid;Kovatich, Albert J.;Ellis, Matthew J.;King, Tari A.;Hu, Hai;Couch, Fergus J.;Mural, Richard J.;Stricker, Thomas;White, Kevin;Olopade, Olufunmilayo;Ingle, James N.;Luo, Chunqing;Chen, Yaqin;Marks, Jeffrey R.;Waldman, Frederic;Wiznerowicz, Maciej;Bose, Ron;Chang, Li-Wei;Beck, Andrew H.;Gonzalez-Angulo, Ana Maria;Pihl, Todd;Jensen, Mark;Sfeir, Robert;Kahn, Ari;Chu, Anna;Kothiyal, Prachi;Wang, Zhining;Snyder, Eric;Pontius, Joan;Ayala, Brenda;Backus, Mark;Walton, Jessica;Baboud, Julien;Berton, Dominique;Nicholls, Matthew;Srinivasan, Deepak;Raman, Rohini;Girshik, Stanley;Kigonya, Peter;Alonso, Shelley;Sanbhadti, Rashmi;Barletta, Sean;Pot, David;Sheth, Margi;Demchok, John A.;Shaw, Kenna R. Mills;Yang, Liming;Eley, Greg;Ferguson, Martin L.;Tarnuzzer, Roy W.;Zhang, Jiashan;Dillon, Laura A. L.;Buetow, Kenneth;Fielding, Peter;Ozenberger, Bradley A.;Guyer, Mark S.;Sofia, Heidi J.;Palchik, Jacqueline D.
我们通过基因组DNA拷贝数阵列、DNA甲基化、外显子组测序、mRNA阵列、microRNA测序和反相蛋白阵列分析原发性乳腺癌。我们跨平台整合信息的能力为先前定义的基因表达亚型提供了关键见解，并在结合来自五个平台的数据时证明了四种主要乳腺癌类别的存在，每个平台都显示出显着的分子异质性。在所有乳腺癌中，仅三种基因（TP 53、PIK 3CA和GATA 3）的体细胞突变发生率> 10%;然而，存在许多亚型相关的新基因突变，包括GATA 3、PIK 3CA和MAP 3 K1中特定突变与管腔A亚型的富集。我们确定了两个新的蛋白质表达定义的亚组，可能由基质/微环境因素贡献，综合分析确定了在每个分子亚型中占主导地位的特定信号传导途径，包括HER 2富集表达亚型中的HER 2/p-HER 2/HER 1/p-HER 1特征。基底细胞样乳腺肿瘤与高级别浆液性卵巢肿瘤的比较显示了许多分子共性，提示了相关的病因学和相似的治疗机会。由遗传和表观遗传异常的不同子集引起的四种主要乳腺癌亚型的生物学发现提出了一个假设，即许多临床上可观察到的可塑性和异质性发生在乳腺癌的这些主要生物学亚型内，而不是跨这些主要生物学亚型。
We analyzed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, mRNA arrays, microRNA sequencing and reverse phase protein arrays. Our ability to integrate information across platforms provided key insights into previously-defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at > 10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the Luminal A subtype. We identified two novel protein expression-defined subgroups, possibly contributed by stromal/microenvironmental elements, and integrated analyses identified specific signaling pathways dominant in each molecular subtype including a HER2/p-HER2/HER1/p-HER1 signature within the HER2-Enriched expression subtype. Comparison of Basal-like breast tumors with high-grade Serous Ovarian tumors showed many molecular commonalities, suggesting a related etiology and similar therapeutic opportunities. The biologic finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biologic subtypes of breast cancer.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
影响因子：
3.6
作者：
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通讯作者：
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影响因子：
64.8
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通讯作者：
Aparicio, Samuel
影响因子：
50.3
作者：
Gewinner C;Wang ZC;Richardson A;Teruya-Feldstein J;Etemadmoghadam D;Bowtell D;Barretina J;Lin WM;Rameh L;Salmena L;Pandolfi PP;Cantley LC
通讯作者：
Cantley LC