Comprehensive molecular portraits of human breast tumours

Daniel C. Koboldt, Robert S. Fulton, Michael D. McLellan, Heather Schmidt, Joelle Kalicki-Veizer, Joshua F. McMichael, Lucinda L. Fulton, David J. Dooling, Li Ding, Elaine R. Mardis, Richard K. Wilson, Adrian Ally, Miruna Balasundaram, Yaron S N Butterfield, Rebecca Carlsen, Candace Carter, Andy Chu, Eric Chuah, Hye Jung E Chun, Robin J N Coope & 323 others Noreen Dhalla, Ranabir Guin, Carrie Hirst, Martin Hirst, Robert A. Holt, Darlene Lee, Haiyan I. Li, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Erin Pleasance, A. Gordon Robertson, Jacqueline E. Schein, Arash Shafiei, Payal Sipahimalani, Jared R. Slobodan, Dominik Stoll, Angela Tam, Nina Thiessen, Richard J. Varhol, Natasja Wye, Thomas Zeng, Yongjun Zhao, Inanc Birol, Steven J M Jones, Marco A. Marra, Andrew D. Cherniack, Gordon Saksena, Robert C. Onofrio, Nam H. Pho, Scott L. Carter, Steven E. Schumacher, Barbara Tabak, Bryan Hernandez, Jeff Gentry, Huy Nguyen, Andrew Crenshaw, Kristin Ardlie, Rameen Beroukhim, Wendy Winckler, Gad Getz, Stacey B. Gabriel, Matthew Meyerson, Lynda Chin, Raju Kucherlapati, Katherine A. Hoadley, J. Todd Auman, Cheng Fan, Yidi J. Turman, Yan Shi, Ling Li, Michael D. Topal, Xiaping He, Hann Hsiang Chao, Aleix Prat, Grace O. Silva, Michael D. Iglesia, Wei Zhao, Jerry Usary, Jonathan S. Berg, Michael Adams, Jessica Booker, Junyuan Wu, Anisha Gulabani, Tom Bodenheimer, Alan P. Hoyle, Janae V. Simons, Matthew G. Soloway, Lisle E. Mose, Stuart R. Jefferys, Saianand Balu, Joel S. Parker, D. Neil Hayes, Charles M. Perou, Simeen Malik, Swapna Mahurkar, Hui Shen, Daniel J. Weisenberger, Timothy Triche, Phillip H. Lai, Moiz S. Bootwalla, Dennis T. Maglinte, Benjamin P. Berman, David J. Van Den Berg, Stephen B. Baylin, Peter W. Laird, Chad J. Creighton, Lawrence A. Donehower, Michael Noble, Doug Voet, Nils Gehlenborg, Daniel Di Cara, Juinhua Zhang, Hailei Zhang, Chang Jiun Wu, Spring Yingchun Liu, Michael S. Lawrence, Lihua Zou, Andrey Sivachenko, Pei Lin, Petar Stojanov, Rui Jing, Juok Cho, Raktim Sinha, Richard W. Park, Marc Danie Nazaire, Jim Robinson, Helga Thorvaldsdottir, Jill Mesirov, Peter J. Park, Sheila Reynolds, Richard B. Kreisberg, Brady Bernard, Ryan Bressler, Timo Erkkila, Jake Lin, Vesteinn Thorsson, Wei Zhang, Ilya Shmulevich, Giovanni Ciriello, Nils Weinhold, Nikolaus Schultz, Jianjiong Gao, Ethan Cerami, Benjamin Gross, Anders Jacobsen, Rileen Sinha, B. Arman Aksoy, Yevgeniy Antipin, Boris Reva, Ronglai Shen, Barry S. Taylor, Marc Ladanyi, Chris Sander, Pavana Anur, Paul T. Spellman, Yiling Lu, Wenbin Liu, Roel R G Verhaak, Gordon B. Mills, Rehan Akbani, Nianxiang Zhang, Bradley M. Broom, Tod D. Casasent, Chris Wakefield, Anna K. Unruh, Keith Baggerly, Kevin Coombes, John N. Weinstein, David Haussler, Christopher C. Benz, Joshua M. Stuart, Stephen C. Benz, Jingchun Zhu, Christopher C. Szeto, Gary K. Scott, Christina Yau, Evan O. Paull, Daniel Carlin, Christopher Wong, Artem Sokolov, Janita Thusberg, Sean Mooney, Sam Ng, Theodore C. Goldstein, Kyle Ellrott, Mia Grifford, Christopher Wilks, Singer Ma, Brian Craft, Chunhua Yan, Ying Hu, Daoud Meerzaman, Julie M. Gastier-Foster, Jay Bowen, Nilsa C. Ramirez, Aaron D. Black, Robert E. Pyatt, Peter White, Erik J. Zmuda, Jessica Frick, Tara M. Lichtenberg, Robin Brookens, Myra M. George, Mark A. Gerken, Hollie A. Harper, Kristen M. Leraas, Lisa J. Wise, Teresa R. Tabler, Cynthia McAllister, Thomas Barr, Melissa Hart-Kothari, Katie Tarvin, Charles Saller, George Sandusky, Colleen Mitchell, Mary V. Iacocca, Jennifer Brown, Brenda Rabeno, Christine Czerwinski, Nicholas Petrelli, Oleg Dolzhansky, Mikhail Abramov, Olga Voronina, Olga Potapova, Jeffrey R. Marks, Wiktoria M. Suchorska, Dawid Murawa, Witold Kycler, Matthew Ibbs, Konstanty Korski, Arkadiusz Spychała, Paweł Murawa, Jacek J. Brzeziński, Hanna Perz, Radosław Łaźniak, Marek Teresiak, Honorata Tatka, Ewa Leporowska, Marta Bogusz-Czerniewicz, Julian Malicki, Andrzej Mackiewicz, Maciej Wiznerowicz, Xuan Van Le, Bernard Kohl, Nguyen Viet Tien, Richard Thorp, Nguyen Van Bang, Howard Sussman, Bui Duc Phu, Richard Hajek, Nguyen Phi Hung, Tran Viet The Phuong, Huynh Quyet Thang, Khurram Zaki Khan, Robert Penny, David Mallery, Erin Curley, Candace Shelton, Peggy Yena, James N. Ingle, Fergus J. Couch, Wilma L. Lingle, Tari A. King, Ana Maria Gonzalez-Angulo, Mary D. Dyer, Shuying Liu, Xiaolong Meng, Modesto Patangan, Frederic Waldman, Hubert Stöppler, W. Kimryn Rathmell, Leigh Thorne, Mei Huang, Lori Boice, Ashley Hill, Carl Morrison, Carmelo Gaudioso, Wiam Bshara, Kelly Daily, Sophie C. Egea, Mark D. Pegram, Carmen Gomez-Fernandez, Rajiv Dhir, Rohit Bhargava, Adam Brufsky, Craig D. Shriver, Jeffrey A. Hooke, Jamie Leigh Campbell, Richard J. Mural, Hai Hu, Stella Somiari, Caroline Larson, Brenda Deyarmin, Leonid Kvecher, Albert J. Kovatich, Matthew J. Ellis, Thomas Stricker, Kevin White, Olufunmilayo Olopade, Chunqing Luo, Yaqin Chen, Ron Bose, Li Wei Chang, Andrew H. Beck, Todd Pihl, Mark Jensen, Robert Sfeir, Ari Kahn, Anna Chu, Prachi Kothiyal, Zhining Wang, Eric Snyder, Joan Pontius, Brenda Ayala, Mark Backus, Jessica Walton, Julien Baboud, Dominique Berton, Matthew Nicholls, Deepak Srinivasan, Rohini Raman, Stanley Girshik, Peter Kigonya, Shelley Alonso, Rashmi Sanbhadti, Sean Barletta, David Pot, Margi Sheth, John A. Demchok, Kenna R Mills Shaw, Liming Yang, Greg Eley, Martin L. Ferguson, Roy W. Tarnuzzer, Jiashan Zhang, Laura A L Dillon, Kenneth Buetow, Peter Fielding, Bradley A. Ozenberger, Mark S. Guyer, Heidi J. Sofia, Jacqueline D. Palchik

Research output: Contribution to journalArticle

4900 Citations (Scopus)

Abstract

We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA 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 produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological 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 biological subtypes of breast cancer.

Original languageEnglish
Pages (from-to)61-70
Number of pages10
JournalNature
Volume490
Issue number7418
DOIs
StatePublished - Oct 4 2012

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Breast Neoplasms
Mutation
Exome
Protein Array Analysis
p53 Genes
DNA Methylation
MicroRNAs
Epigenomics
Gene Expression
Messenger RNA
DNA
Incidence
Genes
Neoplasms
Proteins
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Koboldt, D. C., Fulton, R. S., McLellan, M. D., Schmidt, H., Kalicki-Veizer, J., McMichael, J. F., ... Palchik, J. D. (2012). Comprehensive molecular portraits of human breast tumours. Nature, 490(7418), 61-70. https://doi.org/10.1038/nature11412

Comprehensive molecular portraits of human breast tumours. / 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; Nguyen, Huy; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Getz, Gad; Gabriel, Stacey B.; Meyerson, Matthew; Chin, Lynda; 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; 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.; Noble, Michael; Voet, Doug; Gehlenborg, Nils; Di Cara, Daniel; Zhang, Juinhua; Zhang, Hailei; Wu, Chang Jiun; Yingchun Liu, Spring; 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.; 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; Paull, Evan O.; Carlin, Daniel; Wong, Christopher; Sokolov, Artem; Thusberg, Janita; Mooney, Sean; Ng, Sam; 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, Tara M.; 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; Spychała, Arkadiusz; Murawa, Paweł; Brzeziński, Jacek J.; Perz, Hanna; Łaźniak, Radosław; Teresiak, Marek; Tatka, Honorata; Leporowska, Ewa; Bogusz-Czerniewicz, Marta; Malicki, Julian; Mackiewicz, Andrzej; Wiznerowicz, Maciej; Van Le, Xuan; Kohl, Bernard; Viet Tien, Nguyen; Thorp, Richard; Van Bang, Nguyen; Sussman, Howard; Phu, Bui Duc; Hajek, Richard; Hung, Nguyen Phi; Phuong, Tran Viet The; Thang, Huynh Quyet; 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; Dyer, Mary D.; Liu, Shuying; Meng, Xiaolong; Patangan, Modesto; Waldman, Frederic; Stöppler, 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.; Stricker, Thomas; White, Kevin; Olopade, Olufunmilayo; Luo, Chunqing; Chen, Yaqin; Bose, Ron; Chang, Li Wei; Beck, Andrew H.; 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.

In: Nature, Vol. 490, No. 7418, 04.10.2012, p. 61-70.

Research output: Contribution to journalArticle

Koboldt, DC, Fulton, RS, McLellan, MD, Schmidt, H, Kalicki-Veizer, J, McMichael, JF, Fulton, LL, Dooling, DJ, Ding, L, Mardis, ER, Wilson, RK, Ally, A, Balasundaram, M, Butterfield, YSN, Carlsen, R, Carter, C, Chu, A, Chuah, E, Chun, HJE, Coope, RJN, Dhalla, N, Guin, R, Hirst, C, Hirst, M, Holt, RA, Lee, D, Li, HI, Mayo, M, Moore, RA, Mungall, AJ, Pleasance, E, Robertson, AG, Schein, JE, Shafiei, A, Sipahimalani, P, Slobodan, JR, Stoll, D, Tam, A, Thiessen, N, Varhol, RJ, Wye, N, Zeng, T, Zhao, Y, Birol, I, Jones, SJM, Marra, MA, Cherniack, AD, Saksena, G, Onofrio, RC, Pho, NH, Carter, SL, Schumacher, SE, Tabak, B, Hernandez, B, Gentry, J, Nguyen, H, Crenshaw, A, Ardlie, K, Beroukhim, R, Winckler, W, Getz, G, Gabriel, SB, Meyerson, M, Chin, L, Kucherlapati, R, Hoadley, KA, Auman, JT, Fan, C, Turman, YJ, Shi, Y, Li, L, Topal, MD, He, X, Chao, HH, Prat, A, Silva, GO, Iglesia, MD, Zhao, W, Usary, J, Berg, JS, Adams, M, Booker, J, Wu, J, Gulabani, A, Bodenheimer, T, Hoyle, AP, Simons, JV, Soloway, MG, Mose, LE, Jefferys, SR, Balu, S, Parker, JS, Hayes, DN, Perou, CM, Malik, S, Mahurkar, S, Shen, H, Weisenberger, DJ, Triche, T, Lai, PH, Bootwalla, MS, Maglinte, DT, Berman, BP, Van Den Berg, DJ, Baylin, SB, Laird, PW, Creighton, CJ, Donehower, LA, Noble, M, Voet, D, Gehlenborg, N, Di Cara, D, Zhang, J, Zhang, H, Wu, CJ, Yingchun Liu, S, Lawrence, MS, Zou, L, Sivachenko, A, Lin, P, Stojanov, P, Jing, R, Cho, J, Sinha, R, Park, RW, Nazaire, MD, Robinson, J, Thorvaldsdottir, H, Mesirov, J, Park, PJ, Reynolds, S, Kreisberg, RB, Bernard, B, Bressler, R, Erkkila, T, Lin, J, Thorsson, V, Zhang, W, Shmulevich, I, Ciriello, G, Weinhold, N, Schultz, N, Gao, J, Cerami, E, Gross, B, Jacobsen, A, Sinha, R, Aksoy, BA, Antipin, Y, Reva, B, Shen, R, Taylor, BS, Ladanyi, M, Sander, C, Anur, P, Spellman, PT, Lu, Y, Liu, W, Verhaak, RRG, Mills, GB, Akbani, R, Zhang, N, Broom, BM, Casasent, TD, Wakefield, C, Unruh, AK, Baggerly, K, Coombes, K, Weinstein, JN, Haussler, D, Benz, CC, Stuart, JM, Benz, SC, Zhu, J, Szeto, CC, Scott, GK, Yau, C, Paull, EO, Carlin, D, Wong, C, Sokolov, A, Thusberg, J, Mooney, S, Ng, S, Goldstein, TC, Ellrott, K, Grifford, M, Wilks, C, Ma, S, Craft, B, Yan, C, Hu, Y, Meerzaman, D, Gastier-Foster, JM, Bowen, J, Ramirez, NC, Black, AD, Pyatt, RE, White, P, Zmuda, EJ, Frick, J, Lichtenberg, TM, Brookens, R, George, MM, Gerken, MA, Harper, HA, Leraas, KM, Wise, LJ, Tabler, TR, McAllister, C, Barr, T, Hart-Kothari, M, Tarvin, K, Saller, C, Sandusky, G, Mitchell, C, Iacocca, MV, Brown, J, Rabeno, B, Czerwinski, C, Petrelli, N, Dolzhansky, O, Abramov, M, Voronina, O, Potapova, O, Marks, JR, Suchorska, WM, Murawa, D, Kycler, W, Ibbs, M, Korski, K, Spychała, A, Murawa, P, Brzeziński, JJ, Perz, H, Łaźniak, R, Teresiak, M, Tatka, H, Leporowska, E, Bogusz-Czerniewicz, M, Malicki, J, Mackiewicz, A, Wiznerowicz, M, Van Le, X, Kohl, B, Viet Tien, N, Thorp, R, Van Bang, N, Sussman, H, Phu, BD, Hajek, R, Hung, NP, Phuong, TVT, Thang, HQ, Khan, KZ, Penny, R, Mallery, D, Curley, E, Shelton, C, Yena, P, Ingle, JN, Couch, FJ, Lingle, WL, King, TA, Gonzalez-Angulo, AM, Dyer, MD, Liu, S, Meng, X, Patangan, M, Waldman, F, Stöppler, H, Rathmell, WK, Thorne, L, Huang, M, Boice, L, Hill, A, Morrison, C, Gaudioso, C, Bshara, W, Daily, K, Egea, SC, Pegram, MD, Gomez-Fernandez, C, Dhir, R, Bhargava, R, Brufsky, A, Shriver, CD, Hooke, JA, Campbell, JL, Mural, RJ, Hu, H, Somiari, S, Larson, C, Deyarmin, B, Kvecher, L, Kovatich, AJ, Ellis, MJ, Stricker, T, White, K, Olopade, O, Luo, C, Chen, Y, Bose, R, Chang, LW, Beck, AH, Pihl, T, Jensen, M, Sfeir, R, Kahn, A, Chu, A, Kothiyal, P, Wang, Z, Snyder, E, Pontius, J, Ayala, B, Backus, M, Walton, J, Baboud, J, Berton, D, Nicholls, M, Srinivasan, D, Raman, R, Girshik, S, Kigonya, P, Alonso, S, Sanbhadti, R, Barletta, S, Pot, D, Sheth, M, Demchok, JA, Shaw, KRM, Yang, L, Eley, G, Ferguson, ML, Tarnuzzer, RW, Zhang, J, Dillon, LAL, Buetow, K, Fielding, P, Ozenberger, BA, Guyer, MS, Sofia, HJ & Palchik, JD 2012, 'Comprehensive molecular portraits of human breast tumours', Nature, vol. 490, no. 7418, pp. 61-70. https://doi.org/10.1038/nature11412
Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF et al. Comprehensive molecular portraits of human breast tumours. Nature. 2012 Oct 4;490(7418):61-70. https://doi.org/10.1038/nature11412
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 ; Nguyen, Huy ; Crenshaw, Andrew ; Ardlie, Kristin ; Beroukhim, Rameen ; Winckler, Wendy ; Getz, Gad ; Gabriel, Stacey B. ; Meyerson, Matthew ; Chin, Lynda ; 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 ; 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. ; Noble, Michael ; Voet, Doug ; Gehlenborg, Nils ; Di Cara, Daniel ; Zhang, Juinhua ; Zhang, Hailei ; Wu, Chang Jiun ; Yingchun Liu, Spring ; 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. ; 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 ; Paull, Evan O. ; Carlin, Daniel ; Wong, Christopher ; Sokolov, Artem ; Thusberg, Janita ; Mooney, Sean ; Ng, Sam ; 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, Tara M. ; 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 ; Spychała, Arkadiusz ; Murawa, Paweł ; Brzeziński, Jacek J. ; Perz, Hanna ; Łaźniak, Radosław ; Teresiak, Marek ; Tatka, Honorata ; Leporowska, Ewa ; Bogusz-Czerniewicz, Marta ; Malicki, Julian ; Mackiewicz, Andrzej ; Wiznerowicz, Maciej ; Van Le, Xuan ; Kohl, Bernard ; Viet Tien, Nguyen ; Thorp, Richard ; Van Bang, Nguyen ; Sussman, Howard ; Phu, Bui Duc ; Hajek, Richard ; Hung, Nguyen Phi ; Phuong, Tran Viet The ; Thang, Huynh Quyet ; 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 ; Dyer, Mary D. ; Liu, Shuying ; Meng, Xiaolong ; Patangan, Modesto ; Waldman, Frederic ; Stöppler, 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. ; Stricker, Thomas ; White, Kevin ; Olopade, Olufunmilayo ; Luo, Chunqing ; Chen, Yaqin ; Bose, Ron ; Chang, Li Wei ; Beck, Andrew H. ; 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. / Comprehensive molecular portraits of human breast tumours. In: Nature. 2012 ; Vol. 490, No. 7418. pp. 61-70.
@article{b1959d485da849ad8ba8caa694b3fd32,
title = "Comprehensive molecular portraits of human breast tumours",
abstract = "We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA 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 produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological 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 biological subtypes of breast cancer.",
author = "Koboldt, {Daniel C.} and Fulton, {Robert S.} and McLellan, {Michael D.} and Heather Schmidt and Joelle Kalicki-Veizer and McMichael, {Joshua F.} and Fulton, {Lucinda L.} and Dooling, {David J.} and Li Ding and Mardis, {Elaine R.} and Wilson, {Richard K.} and Adrian Ally and Miruna Balasundaram and Butterfield, {Yaron S N} and Rebecca Carlsen and Candace Carter and Andy Chu and Eric Chuah and Chun, {Hye Jung E} and Coope, {Robin J N} and Noreen Dhalla and Ranabir Guin and Carrie Hirst and Martin Hirst and Holt, {Robert A.} and Darlene Lee and Li, {Haiyan I.} and Michael Mayo and Moore, {Richard A.} and Mungall, {Andrew J.} and Erin Pleasance and Robertson, {A. Gordon} and Schein, {Jacqueline E.} and Arash Shafiei and Payal Sipahimalani and Slobodan, {Jared R.} and Dominik Stoll and Angela Tam and Nina Thiessen and Varhol, {Richard J.} and Natasja Wye and Thomas Zeng and Yongjun Zhao and Inanc Birol and Jones, {Steven J M} and Marra, {Marco A.} and Cherniack, {Andrew D.} and Gordon Saksena and Onofrio, {Robert C.} and Pho, {Nam H.} and Carter, {Scott L.} and Schumacher, {Steven E.} and Barbara Tabak and Bryan Hernandez and Jeff Gentry and Huy Nguyen and Andrew Crenshaw and Kristin Ardlie and Rameen Beroukhim and Wendy Winckler and Gad Getz and Gabriel, {Stacey B.} and Matthew Meyerson and Lynda Chin and Raju Kucherlapati and Hoadley, {Katherine A.} and Auman, {J. Todd} and Cheng Fan and Turman, {Yidi J.} and Yan Shi and Ling Li and Topal, {Michael D.} and Xiaping He and Chao, {Hann Hsiang} and Aleix Prat and Silva, {Grace O.} and Iglesia, {Michael D.} and Wei Zhao and Jerry Usary and Berg, {Jonathan S.} and Michael Adams and Jessica Booker and Junyuan Wu and Anisha Gulabani and Tom Bodenheimer and Hoyle, {Alan P.} and Simons, {Janae V.} and Soloway, {Matthew G.} and Mose, {Lisle E.} and Jefferys, {Stuart R.} and Saianand Balu and Parker, {Joel S.} and Hayes, {D. Neil} and Perou, {Charles M.} and Simeen Malik and Swapna Mahurkar and Hui Shen and Weisenberger, {Daniel J.} and Timothy Triche and Lai, {Phillip H.} and Bootwalla, {Moiz S.} and Maglinte, {Dennis T.} and Berman, {Benjamin P.} and {Van Den Berg}, {David J.} and Baylin, {Stephen B.} and Laird, {Peter W.} and Creighton, {Chad J.} and Donehower, {Lawrence A.} and Michael Noble and Doug Voet and Nils Gehlenborg and {Di Cara}, Daniel and Juinhua Zhang and Hailei Zhang and Wu, {Chang Jiun} and {Yingchun Liu}, Spring and Lawrence, {Michael S.} and Lihua Zou and Andrey Sivachenko and Pei Lin and Petar Stojanov and Rui Jing and Juok Cho and Raktim Sinha and Park, {Richard W.} and Nazaire, {Marc Danie} and Jim Robinson and Helga Thorvaldsdottir and Jill Mesirov and Park, {Peter J.} and Sheila Reynolds and Kreisberg, {Richard B.} and Brady Bernard and Ryan Bressler and Timo Erkkila and Jake Lin and Vesteinn Thorsson and Wei Zhang and Ilya Shmulevich and Giovanni Ciriello and Nils Weinhold and Nikolaus Schultz and Jianjiong Gao and Ethan Cerami and Benjamin Gross and Anders Jacobsen and Rileen Sinha and Aksoy, {B. Arman} and Yevgeniy Antipin and Boris Reva and Ronglai Shen and Taylor, {Barry S.} and Marc Ladanyi and Chris Sander and Pavana Anur and Spellman, {Paul T.} and Yiling Lu and Wenbin Liu and Verhaak, {Roel R G} and Mills, {Gordon B.} and Rehan Akbani and Nianxiang Zhang and Broom, {Bradley M.} and Casasent, {Tod D.} and Chris Wakefield and Unruh, {Anna K.} and Keith Baggerly and Kevin Coombes and Weinstein, {John N.} and David Haussler and Benz, {Christopher C.} and Stuart, {Joshua M.} and Benz, {Stephen C.} and Jingchun Zhu and Szeto, {Christopher C.} and Scott, {Gary K.} and Christina Yau and Paull, {Evan O.} and Daniel Carlin and Christopher Wong and Artem Sokolov and Janita Thusberg and Sean Mooney and Sam Ng and Goldstein, {Theodore C.} and Kyle Ellrott and Mia Grifford and Christopher Wilks and Singer Ma and Brian Craft and Chunhua Yan and Ying Hu and Daoud Meerzaman and Gastier-Foster, {Julie M.} and Jay Bowen and Ramirez, {Nilsa C.} and Black, {Aaron D.} and Pyatt, {Robert E.} and Peter White and Zmuda, {Erik J.} and Jessica Frick and Lichtenberg, {Tara M.} and Robin Brookens and George, {Myra M.} and Gerken, {Mark A.} and Harper, {Hollie A.} and Leraas, {Kristen M.} and Wise, {Lisa J.} and Tabler, {Teresa R.} and Cynthia McAllister and Thomas Barr and Melissa Hart-Kothari and Katie Tarvin and Charles Saller and George Sandusky and Colleen Mitchell and Iacocca, {Mary V.} and Jennifer Brown and Brenda Rabeno and Christine Czerwinski and Nicholas Petrelli and Oleg Dolzhansky and Mikhail Abramov and Olga Voronina and Olga Potapova and Marks, {Jeffrey R.} and Suchorska, {Wiktoria M.} and Dawid Murawa and Witold Kycler and Matthew Ibbs and Konstanty Korski and Arkadiusz Spychała and Paweł Murawa and Brzeziński, {Jacek J.} and Hanna Perz and Radosław Łaźniak and Marek Teresiak and Honorata Tatka and Ewa Leporowska and Marta Bogusz-Czerniewicz and Julian Malicki and Andrzej Mackiewicz and Maciej Wiznerowicz and {Van Le}, Xuan and Bernard Kohl and {Viet Tien}, Nguyen and Richard Thorp and {Van Bang}, Nguyen and Howard Sussman and Phu, {Bui Duc} and Richard Hajek and Hung, {Nguyen Phi} and Phuong, {Tran Viet The} and Thang, {Huynh Quyet} and Khan, {Khurram Zaki} and Robert Penny and David Mallery and Erin Curley and Candace Shelton and Peggy Yena and Ingle, {James N.} and Couch, {Fergus J.} and Lingle, {Wilma L.} and King, {Tari A.} and Gonzalez-Angulo, {Ana Maria} and Dyer, {Mary D.} and Shuying Liu and Xiaolong Meng and Modesto Patangan and Frederic Waldman and Hubert St{\"o}ppler and Rathmell, {W. Kimryn} and Leigh Thorne and Mei Huang and Lori Boice and Ashley Hill and Carl Morrison and Carmelo Gaudioso and Wiam Bshara and Kelly Daily and Egea, {Sophie C.} and Pegram, {Mark D.} and Carmen Gomez-Fernandez and Rajiv Dhir and Rohit Bhargava and Adam Brufsky and Shriver, {Craig D.} and Hooke, {Jeffrey A.} and Campbell, {Jamie Leigh} and Mural, {Richard J.} and Hai Hu and Stella Somiari and Caroline Larson and Brenda Deyarmin and Leonid Kvecher and Kovatich, {Albert J.} and Ellis, {Matthew J.} and Thomas Stricker and Kevin White and Olufunmilayo Olopade and Chunqing Luo and Yaqin Chen and Ron Bose and Chang, {Li Wei} and Beck, {Andrew H.} and Todd Pihl and Mark Jensen and Robert Sfeir and Ari Kahn and Anna Chu and Prachi Kothiyal and Zhining Wang and Eric Snyder and Joan Pontius and Brenda Ayala and Mark Backus and Jessica Walton and Julien Baboud and Dominique Berton and Matthew Nicholls and Deepak Srinivasan and Rohini Raman and Stanley Girshik and Peter Kigonya and Shelley Alonso and Rashmi Sanbhadti and Sean Barletta and David Pot and Margi Sheth and Demchok, {John A.} and Shaw, {Kenna R Mills} and Liming Yang and Greg Eley and Ferguson, {Martin L.} and Tarnuzzer, {Roy W.} and Jiashan Zhang and Dillon, {Laura A L} and Kenneth Buetow and Peter Fielding and Ozenberger, {Bradley A.} and Guyer, {Mark S.} and Sofia, {Heidi J.} and Palchik, {Jacqueline D.}",
year = "2012",
month = "10",
day = "4",
doi = "10.1038/nature11412",
language = "English",
volume = "490",
pages = "61--70",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7418",

}

TY - JOUR

T1 - Comprehensive molecular portraits of human breast tumours

AU - Koboldt, Daniel C.

AU - Fulton, Robert S.

AU - McLellan, Michael D.

AU - Schmidt, Heather

AU - Kalicki-Veizer, Joelle

AU - McMichael, Joshua F.

AU - Fulton, Lucinda L.

AU - Dooling, David J.

AU - Ding, Li

AU - Mardis, Elaine R.

AU - Wilson, Richard K.

AU - Ally, Adrian

AU - Balasundaram, Miruna

AU - Butterfield, Yaron S N

AU - Carlsen, Rebecca

AU - Carter, Candace

AU - Chu, Andy

AU - Chuah, Eric

AU - Chun, Hye Jung E

AU - Coope, Robin J N

AU - Dhalla, Noreen

AU - Guin, Ranabir

AU - Hirst, Carrie

AU - Hirst, Martin

AU - Holt, Robert A.

AU - Lee, Darlene

AU - Li, Haiyan I.

AU - Mayo, Michael

AU - Moore, Richard A.

AU - Mungall, Andrew J.

AU - Pleasance, Erin

AU - Robertson, A. Gordon

AU - Schein, Jacqueline E.

AU - Shafiei, Arash

AU - Sipahimalani, Payal

AU - Slobodan, Jared R.

AU - Stoll, Dominik

AU - Tam, Angela

AU - Thiessen, Nina

AU - Varhol, Richard J.

AU - Wye, Natasja

AU - Zeng, Thomas

AU - Zhao, Yongjun

AU - Birol, Inanc

AU - Jones, Steven J M

AU - Marra, Marco A.

AU - Cherniack, Andrew D.

AU - Saksena, Gordon

AU - Onofrio, Robert C.

AU - Pho, Nam H.

AU - Carter, Scott L.

AU - Schumacher, Steven E.

AU - Tabak, Barbara

AU - Hernandez, Bryan

AU - Gentry, Jeff

AU - Nguyen, Huy

AU - Crenshaw, Andrew

AU - Ardlie, Kristin

AU - Beroukhim, Rameen

AU - Winckler, Wendy

AU - Getz, Gad

AU - Gabriel, Stacey B.

AU - Meyerson, Matthew

AU - Chin, Lynda

AU - Kucherlapati, Raju

AU - Hoadley, Katherine A.

AU - Auman, J. Todd

AU - Fan, Cheng

AU - Turman, Yidi J.

AU - Shi, Yan

AU - Li, Ling

AU - Topal, Michael D.

AU - He, Xiaping

AU - Chao, Hann Hsiang

AU - Prat, Aleix

AU - Silva, Grace O.

AU - Iglesia, Michael D.

AU - Zhao, Wei

AU - Usary, Jerry

AU - Berg, Jonathan S.

AU - Adams, Michael

AU - Booker, Jessica

AU - Wu, Junyuan

AU - Gulabani, Anisha

AU - Bodenheimer, Tom

AU - Hoyle, Alan P.

AU - Simons, Janae V.

AU - Soloway, Matthew G.

AU - Mose, Lisle E.

AU - Jefferys, Stuart R.

AU - Balu, Saianand

AU - Parker, Joel S.

AU - Hayes, D. Neil

AU - Perou, Charles M.

AU - Malik, Simeen

AU - Mahurkar, Swapna

AU - Shen, Hui

AU - Weisenberger, Daniel J.

AU - Triche, Timothy

AU - Lai, Phillip H.

AU - Bootwalla, Moiz S.

AU - Maglinte, Dennis T.

AU - Berman, Benjamin P.

AU - Van Den Berg, David J.

AU - Baylin, Stephen B.

AU - Laird, Peter W.

AU - Creighton, Chad J.

AU - Donehower, Lawrence A.

AU - Noble, Michael

AU - Voet, Doug

AU - Gehlenborg, Nils

AU - Di Cara, Daniel

AU - Zhang, Juinhua

AU - Zhang, Hailei

AU - Wu, Chang Jiun

AU - Yingchun Liu, Spring

AU - Lawrence, Michael S.

AU - Zou, Lihua

AU - Sivachenko, Andrey

AU - Lin, Pei

AU - Stojanov, Petar

AU - Jing, Rui

AU - Cho, Juok

AU - Sinha, Raktim

AU - Park, Richard W.

AU - Nazaire, Marc Danie

AU - Robinson, Jim

AU - Thorvaldsdottir, Helga

AU - Mesirov, Jill

AU - Park, Peter J.

AU - Reynolds, Sheila

AU - Kreisberg, Richard B.

AU - Bernard, Brady

AU - Bressler, Ryan

AU - Erkkila, Timo

AU - Lin, Jake

AU - Thorsson, Vesteinn

AU - Zhang, Wei

AU - Shmulevich, Ilya

AU - Ciriello, Giovanni

AU - Weinhold, Nils

AU - Schultz, Nikolaus

AU - Gao, Jianjiong

AU - Cerami, Ethan

AU - Gross, Benjamin

AU - Jacobsen, Anders

AU - Sinha, Rileen

AU - Aksoy, B. Arman

AU - Antipin, Yevgeniy

AU - Reva, Boris

AU - Shen, Ronglai

AU - Taylor, Barry S.

AU - Ladanyi, Marc

AU - Sander, Chris

AU - Anur, Pavana

AU - Spellman, Paul T.

AU - Lu, Yiling

AU - Liu, Wenbin

AU - Verhaak, Roel R G

AU - Mills, Gordon B.

AU - Akbani, Rehan

AU - Zhang, Nianxiang

AU - Broom, Bradley M.

AU - Casasent, Tod D.

AU - Wakefield, Chris

AU - Unruh, Anna K.

AU - Baggerly, Keith

AU - Coombes, Kevin

AU - Weinstein, John N.

AU - Haussler, David

AU - Benz, Christopher C.

AU - Stuart, Joshua M.

AU - Benz, Stephen C.

AU - Zhu, Jingchun

AU - Szeto, Christopher C.

AU - Scott, Gary K.

AU - Yau, Christina

AU - Paull, Evan O.

AU - Carlin, Daniel

AU - Wong, Christopher

AU - Sokolov, Artem

AU - Thusberg, Janita

AU - Mooney, Sean

AU - Ng, Sam

AU - Goldstein, Theodore C.

AU - Ellrott, Kyle

AU - Grifford, Mia

AU - Wilks, Christopher

AU - Ma, Singer

AU - Craft, Brian

AU - Yan, Chunhua

AU - Hu, Ying

AU - Meerzaman, Daoud

AU - Gastier-Foster, Julie M.

AU - Bowen, Jay

AU - Ramirez, Nilsa C.

AU - Black, Aaron D.

AU - Pyatt, Robert E.

AU - White, Peter

AU - Zmuda, Erik J.

AU - Frick, Jessica

AU - Lichtenberg, Tara M.

AU - Brookens, Robin

AU - George, Myra M.

AU - Gerken, Mark A.

AU - Harper, Hollie A.

AU - Leraas, Kristen M.

AU - Wise, Lisa J.

AU - Tabler, Teresa R.

AU - McAllister, Cynthia

AU - Barr, Thomas

AU - Hart-Kothari, Melissa

AU - Tarvin, Katie

AU - Saller, Charles

AU - Sandusky, George

AU - Mitchell, Colleen

AU - Iacocca, Mary V.

AU - Brown, Jennifer

AU - Rabeno, Brenda

AU - Czerwinski, Christine

AU - Petrelli, Nicholas

AU - Dolzhansky, Oleg

AU - Abramov, Mikhail

AU - Voronina, Olga

AU - Potapova, Olga

AU - Marks, Jeffrey R.

AU - Suchorska, Wiktoria M.

AU - Murawa, Dawid

AU - Kycler, Witold

AU - Ibbs, Matthew

AU - Korski, Konstanty

AU - Spychała, Arkadiusz

AU - Murawa, Paweł

AU - Brzeziński, Jacek J.

AU - Perz, Hanna

AU - Łaźniak, Radosław

AU - Teresiak, Marek

AU - Tatka, Honorata

AU - Leporowska, Ewa

AU - Bogusz-Czerniewicz, Marta

AU - Malicki, Julian

AU - Mackiewicz, Andrzej

AU - Wiznerowicz, Maciej

AU - Van Le, Xuan

AU - Kohl, Bernard

AU - Viet Tien, Nguyen

AU - Thorp, Richard

AU - Van Bang, Nguyen

AU - Sussman, Howard

AU - Phu, Bui Duc

AU - Hajek, Richard

AU - Hung, Nguyen Phi

AU - Phuong, Tran Viet The

AU - Thang, Huynh Quyet

AU - Khan, Khurram Zaki

AU - Penny, Robert

AU - Mallery, David

AU - Curley, Erin

AU - Shelton, Candace

AU - Yena, Peggy

AU - Ingle, James N.

AU - Couch, Fergus J.

AU - Lingle, Wilma L.

AU - King, Tari A.

AU - Gonzalez-Angulo, Ana Maria

AU - Dyer, Mary D.

AU - Liu, Shuying

AU - Meng, Xiaolong

AU - Patangan, Modesto

AU - Waldman, Frederic

AU - Stöppler, Hubert

AU - Rathmell, W. Kimryn

AU - Thorne, Leigh

AU - Huang, Mei

AU - Boice, Lori

AU - Hill, Ashley

AU - Morrison, Carl

AU - Gaudioso, Carmelo

AU - Bshara, Wiam

AU - Daily, Kelly

AU - Egea, Sophie C.

AU - Pegram, Mark D.

AU - Gomez-Fernandez, Carmen

AU - Dhir, Rajiv

AU - Bhargava, Rohit

AU - Brufsky, Adam

AU - Shriver, Craig D.

AU - Hooke, Jeffrey A.

AU - Campbell, Jamie Leigh

AU - Mural, Richard J.

AU - Hu, Hai

AU - Somiari, Stella

AU - Larson, Caroline

AU - Deyarmin, Brenda

AU - Kvecher, Leonid

AU - Kovatich, Albert J.

AU - Ellis, Matthew J.

AU - Stricker, Thomas

AU - White, Kevin

AU - Olopade, Olufunmilayo

AU - Luo, Chunqing

AU - Chen, Yaqin

AU - Bose, Ron

AU - Chang, Li Wei

AU - Beck, Andrew H.

AU - Pihl, Todd

AU - Jensen, Mark

AU - Sfeir, Robert

AU - Kahn, Ari

AU - Chu, Anna

AU - Kothiyal, Prachi

AU - Wang, Zhining

AU - Snyder, Eric

AU - Pontius, Joan

AU - Ayala, Brenda

AU - Backus, Mark

AU - Walton, Jessica

AU - Baboud, Julien

AU - Berton, Dominique

AU - Nicholls, Matthew

AU - Srinivasan, Deepak

AU - Raman, Rohini

AU - Girshik, Stanley

AU - Kigonya, Peter

AU - Alonso, Shelley

AU - Sanbhadti, Rashmi

AU - Barletta, Sean

AU - Pot, David

AU - Sheth, Margi

AU - Demchok, John A.

AU - Shaw, Kenna R Mills

AU - Yang, Liming

AU - Eley, Greg

AU - Ferguson, Martin L.

AU - Tarnuzzer, Roy W.

AU - Zhang, Jiashan

AU - Dillon, Laura A L

AU - Buetow, Kenneth

AU - Fielding, Peter

AU - Ozenberger, Bradley A.

AU - Guyer, Mark S.

AU - Sofia, Heidi J.

AU - Palchik, Jacqueline D.

PY - 2012/10/4

Y1 - 2012/10/4

N2 - We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA 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 produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological 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 biological subtypes of breast cancer.

AB - We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA 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 produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological 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 biological subtypes of breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=84877028141&partnerID=8YFLogxK

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U2 - 10.1038/nature11412

DO - 10.1038/nature11412

M3 - Article

VL - 490

SP - 61

EP - 70

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7418

ER -