Sequence analysis of mutations and translocations across breast cancer subtypes

被引：944

作者：

Banerji, Shantanu ^{[1
,2
,3
]}

Cibulskis, Kristian ^{[1
]}

Rangel-Escareno, Claudia ^{[4
]}

Brown, Kristin K. ^{[5
]}

Carter, Scott L. ^{[1
]}

Frederick, Abbie M. ^{[1
]}

Lawrence, Michael S. ^{[1
]}

Sivachenko, Andrey Y. ^{[1
]}

Sougnez, Carrie ^{[1
]}

Zou, Lihua ^{[1
]}

Cortes, Maria L. ^{[1
]}

Fernandez-Lopez, Juan C. ^{[4
]}

Peng, Shouyong ^{[2
]}

Ardlie, Kristin G. ^{[1
]}

Auclair, Daniel ^{[1
]}

Bautista-Pina, Veronica ^{[6
]}

Duke, Fujiko ^{[1
]}

Francis, Joshua ^{[1
]}

Jung, Joonil ^{[1
]}

Maffuz-Aziz, Antonio ^{[6
]}

Onofrio, Robert C. ^{[1
]}

Parkin, Melissa ^{[1
]}

Pho, Nam H. ^{[1
]}

Quintanar-Jurado, Valeria ^{[4
]}

Ramos, Alex H. ^{[1
]}

Rebollar-Vega, Rosa ^{[4
]}

Rodriguez-Cuevas, Sergio ^{[6
]}

Romero-Cordoba, Sandra L. ^{[4
]}

Schumacher, Steven E. ^{[1
,2
]}

Stransky, Nicolas ^{[1
]}

Thompson, Kristin M. ^{[1
]}

Uribe-Figueroa, Laura ^{[4
]}

Baselga, Jose ^{[3
,7
]}

Beroukhim, Rameen ^{[1
,2
,3
,8
]}

Polyak, Kornelia ^{[2
,3
,9
]}

Sgroi, Dennis C. ^{[3
,10
]}

Richardson, Andrea L. ^{[2
,3
,11
]}

Jimenez-Sanchez, Gerardo ^{[4
]}

Lander, Eric S. ^{[1
,3
,12
]}

Gabriel, Stacey B. ^{[1
]}

Garraway, Levi A. ^{[1
,2
,3
]}

Golub, Todd R. ^{[1
,3
,13
,14
]}

Melendez-Zajgla, Jorge ^{[4
]}

Toker, Alex ^{[3
,5
]}

Getz, Gad ^{[1
]}

Hidalgo-Miranda, Alfredo ^{[4
]}

Meyerson, Matthew ^{[1
,2
,3
,8
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[3] Harvard Univ, Sch Med, Boston, MA 02115 USA

[4] Inst Nacl Med Genom, Mexico City 01900, DF, Mexico

[5] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA

[6] FUCAM, Inst Enfermedades Mama, Mexico City 04980, DF, Mexico

[7] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA

[8] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[9] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[10] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[11] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[12] MIT, Cambridge, MA 02139 USA

[13] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA

[14] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

NATURE | 2012年 / 486卷 / 7403期

关键词：

HIGH-FREQUENCY; PIK3CA GENE; GENOME; LANDSCAPES; PATTERNS; FUSION; DOMAIN; KINASE;

D O I：

10.1038/nature11154

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Breast carcinoma is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.38 million new cases and 458,000 deaths in 2008 alone(1). This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis and responses to available therapy(2-4). Recurrent somatic alterations in breast cancer have been described, including mutations and copy number alterations, notably ERBB2 amplifications, the first successful therapy target defined by a genomic aberration(5). Previous DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements(6-10). Here we report the whole-exome sequences of DNA from 103 human breast cancers of diverse subtypes from patients in Mexico and Vietnam compared to matched-normal DNA, together with whole-genome sequences of 22 breast cancer/normal pairs. Beyond confirming recurrent somatic mutations in PIK3CA(11), TP53(6), AKT1(12), GATA3(13) and MAP3K1(10), we discovered recurrent mutations in the CBFB transcription factor gene and deletions of its partner RUNX1. Furthermore, we have identified a recurrent MAGI3-AKT3 fusion enriched in triple-negative breast cancer lacking oestrogen and progesterone receptors and ERBB2 expression. The MAGI3-AKT3 fusion leads to constitutive activation of AKT kinase, which is abolished by treatment with an ATP-competitive AKT small-molecule inhibitor.

引用

页码：405 / 409

页数：5

共 29 条

[1] The PIK3CA gene is mutated with high frequency in human breast cancers [J].

Bachman, KE ;

Argani, P ;

Samuels, Y ;

Silliman, N ;

Ptak, J ;

Szabo, S ;

Konishi, H ;

Karakas, B ;

Blair, BG ;

Lin, C ;

Peters, BA ;

Velculescu, VE ;

Park, BH .

CANCER BIOLOGY & THERAPY, 2004, 3 (08) :772-775

[2] The genomic complexity of primary human prostate cancer [J].

Berger, Michael F. ;

Lawrence, Michael S. ;

Demichelis, Francesca ;

Drier, Yotam ;

Cibulskis, Kristian ;

Sivachenko, Andrey Y. ;

Sboner, Andrea ;

Esgueva, Raquel ;

Pflueger, Dorothee ;

Sougnez, Carrie ;

Onofrio, Robert ;

Carter, Scott L. ;

Park, Kyung ;

Habegger, Lukas ;

Ambrogio, Lauren ;

Fennell, Timothy ;

Parkin, Melissa ;

Saksena, Gordon ;

Voet, Douglas ;

Ramos, Alex H. ;

Pugh, Trevor J. ;

Wilkinson, Jane ;

Fisher, Sheila ;

Winckler, Wendy ;

Mahan, Scott ;

Ardlie, Kristin ;

Baldwin, Jennifer ;

Simons, Jonathan W. ;

Kitabayashi, Naoki ;

MacDonald, Theresa Y. ;

Kantoff, Philip W. ;

Chin, Lynda ;

Gabriel, Stacey B. ;

Gerstein, Mark B. ;

Golub, Todd R. ;

Meyerson, Matthew ;

Tewari, Ashutosh ;

Lander, Eric S. ;

Getz, Gad ;

Rubin, Mark A. ;

Garraway, Levi A. .

NATURE, 2011, 470 (7333) :214-220

[3] The Runx genes:: lineage-specific oncogenes and tumor suppressors [J].

Cameron, ER ;

Neil, JC .

ONCOGENE, 2004, 23 (24) :4308-4314

[4] A transforming mutation in the pleckstrin homology domain of AKT1 in cancer [J].

Carpten, John D. ;

Faber, Andrew L. ;

Horn, Candice ;

Donoho, Gregory P. ;

Briggs, Stephen L. ;

Robbins, Christiane M. ;

Hostetter, Galen ;

Boguslawski, Sophie ;

Moses, Tracy Y. ;

Savage, Stephanie ;

Uhlik, Mark ;

Lin, Aimin ;

Du, Jian ;

Qian, Yue-Wei ;

Zeckner, Douglas J. ;

Tucker-Kellogg, Greg ;

Touchman, Jeffrey ;

Patel, Ketan ;

Mousses, Spyro ;

Bittner, Michael ;

Schevitz, Richard ;

Lai, Mei-Huei T. ;

Blanchard, Kerry L. ;

Thomas, James E. .

NATURE, 2007, 448 (7152) :439-U1

[5] Absolute quantification of somatic DNA alterations in human cancer [J].

Carter, Scott L. ;

Cibulskis, Kristian ;

Helman, Elena ;

McKenna, Aaron ;

Shen, Hui ;

Zack, Travis ;

Laird, Peter W. ;

Onofrio, Robert C. ;

Winckler, Wendy ;

Weir, Barbara A. ;

Beroukhim, Rameen ;

Pellman, David ;

Levine, Douglas A. ;

Lander, Eric S. ;

Meyerson, Matthew ;

Getz, Gad .

NATURE BIOTECHNOLOGY, 2012, 30 (05) :413-+

[6] Initial genome sequencing and analysis of multiple myeloma [J].

Chapman, Michael A. ;

Lawrence, Michael S. ;

Keats, Jonathan J. ;

Cibulskis, Kristian ;

Sougnez, Carrie ;

Schinzel, Anna C. ;

Harview, Christina L. ;

Brunet, Jean-Philippe ;

Ahmann, Gregory J. ;

Adli, Mazhar ;

Anderson, Kenneth C. ;

Ardlie, Kristin G. ;

Auclair, Daniel ;

Baker, Angela ;

Bergsagel, P. Leif ;

Bernstein, Bradley E. ;

Drier, Yotam ;

Fonseca, Rafael ;

Gabriel, Stacey B. ;

Hofmeister, Craig C. ;

Jagannath, Sundar ;

Jakubowiak, Andrzej J. ;

Krishnan, Amrita ;

Levy, Joan ;

Liefeld, Ted ;

Lonial, Sagar ;

Mahan, Scott ;

Mfuko, Bunmi ;

Monti, Stefano ;

Perkins, Louise M. ;

Onofrio, Robb ;

Pugh, Trevor J. ;

Rajkumar, S. Vincent ;

Ramos, Alex H. ;

Siegel, David S. ;

Sivachenko, Andrey ;

Stewart, A. Keith ;

Trudel, Suzanne ;

Vij, Ravi ;

Voet, Douglas ;

Winckler, Wendy ;

Zimmerman, Todd ;

Carpten, John ;

Trent, Jeff ;

Hahn, William C. ;

Garraway, Levi A. ;

Meyerson, Matthew ;

Lander, Eric S. ;

Getz, Gad ;

Golub, Todd R. .

NATURE, 2011, 471 (7339) :467-472

[7] Genomic and transcriptional aberrations linked to breast cancer pathophysiologies [J].

Chin, Koei ;

DeVries, Sandy ;

Fridlyand, Jane ;

Spellman, Paul T. ;

Roydasgupta, Ritu ;

Kuo, Wen-Lin ;

Lapuk, Anna ;

Neve, Richard M. ;

Qian, Zuwei ;

Ryder, Tom ;

Chen, Fanqing ;

Feiler, Heidi ;

Tokuyasu, Taku ;

Kingsley, Chris ;

Dairkee, Shanaz ;

Meng, Zhenhang ;

Chew, Karen ;

Pinkel, Daniel ;

Jain, Ajay ;

Ljung, Britt Marie ;

Esserman, Laura ;

Albertson, Donna G. ;

Waldman, Frederic M. ;

Gray, Joe W. .

CANCER CELL, 2006, 10 (06) :529-541

[8] Genome remodelling in a basal-like breast cancer metastasis and xenograft [J].

Ding, Li ;

Ellis, Matthew J. ;

Li, Shunqiang ;

Larson, David E. ;

Chen, Ken ;

Wallis, Johnw. ;

Harris, Christopher C. ;

McLellan, Michael D. ;

Fulton, Robert S. ;

Fulton, Lucinda L. ;

Abbott, Rachel M. ;

Hoog, Jeremy ;

Dooling, David J. ;

Koboldt, Daniel C. ;

Schmidt, Heather ;

Kalicki, Joelle ;

Zhang, Qunyuan ;

Chen, Lei ;

Lin, Ling ;

Wendl, Michael C. ;

McMichael, Joshua F. ;

Magrini, Vincent J. ;

Cook, Lisa ;

McGrath, Sean D. ;

Vickery, Tammi L. ;

Appelbaum, Elizabeth ;

DeSchryver, Katherine ;

Davies, Sherri ;

Guintoli, Therese ;

Lin, Li ;

Crowder, Robert ;

Tao, Yu ;

Snider, Jacqueline E. ;

Smith, Scott M. ;

Dukes, Adam F. ;

Sanderson, Gabriel E. ;

Pohl, Craig S. ;

Delehaunty, Kim D. ;

Fronick, Catrina C. ;

Pape, Kimberley A. ;

Reed, Jerry S. ;

Robinson, Jody S. ;

Hodges, Jennifer S. ;

Schierding, William ;

Dees, Nathan D. ;

Shen, Dong ;

Locke, Devin P. ;

Wiechert, Madeline E. ;

Eldred, James M. ;

Peck, Josh B. .

NATURE, 2010, 464 (7291) :999-1005

[9] A pathway-based classification of human breast cancer [J].

Gatza, Michael L. ;

Lucas, Joseph E. ;

Barry, William T. ;

Kim, Jong Wook ;

Wang, Quanli ;

Crawford, Matthew D. ;

Datto, Michael B. ;

Kelley, Michael ;

Mathey-Prevot, Bernard ;

Potti, Anil ;

Nevins, Joseph R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (15) :6994-6999

[10] Diverse somatic mutation patterns and pathway alterations in human cancers [J].

Kan, Zhengyan ;

Jaiswal, Bijay S. ;

Stinson, Jeremy ;

Janakiraman, Vasantharajan ;

Bhatt, Deepali ;

Stern, Howard M. ;

Yue, Peng ;

Haverty, Peter M. ;

Bourgon, Richard ;

Zheng, Jianbiao ;

Moorhead, Martin ;

Chaudhuri, Subhra ;

Tomsho, Lynn P. ;

Peters, Brock A. ;

Pujara, Kanan ;

Cordes, Shaun ;

Davis, David P. ;

Carlton, Victoria E. H. ;

Yuan, Wenlin ;

Li, Li ;

Wang, Weiru ;

Eigenbrot, Charles ;

Kaminker, Joshua S. ;

Eberhard, David A. ;

Waring, Paul ;

Schuster, Stephan C. ;

Modrusan, Zora ;

Zhang, Zemin ;

Stokoe, David ;

de Sauvage, Frederic J. ;

Faham, Malek ;

Seshagiri, Somasekar .

NATURE, 2010, 466 (7308) :869-U103

← 1 2 3 →