Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2

被引：235

作者：

Greulich, Heidi ^{[1
,3
,5
,6
]}

Kaplan, Bethany ^{[1
,6
]}

Mertins, Philipp ^{[6
]}

Chen, Tzu-Hsiu ^{[6
]}

Tanaka, Kumiko E. ^{[1
,6
]}

Yun, Cai-Hong ^{[7
]}

Zhang, Xiaohong ^{[1
]}

Lee, Se-Hoon ^{[1
]}

Cho, Jeonghee ^{[1
]}

Ambrogio, Lauren ^{[6
]}

Liao, Rachel ^{[1
,6
]}

Imielinski, Marcin ^{[1
,6
]}

Banerji, Shantanu ^{[1
,6
]}

Berger, Alice H. ^{[1
,6
]}

Lawrence, Michael S. ^{[6
]}

Zhang, Jinghui ^{[8
,9
]}

Pho, Nam H. ^{[1
,6
]}

Walker, Sarah R. ^{[1
]}

Winckler, Wendy ^{[6
]}

Getz, Gad ^{[6
]}

Frank, David ^{[1
]}

Hahn, William C. ^{[1
,2
,3
,6
]}

Eck, Michael J.

Mani, D. R. ^{[6
]}

Jaffe, Jacob D. ^{[6
]}

Carr, Steven A. ^{[6
]}

Wong, Kwok-Kin ^{[1
,3
,5
]}

Meyerson, Matthew ^{[1
,2
,4
,6
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

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

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

[5] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

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

[7] Peking Univ, Hlth Sci Ctr, Dept Biophys, Beijing 100191, Peoples R China

[8] St Jude Childrens Res Hosp, Dept Biotechnol, Memphis, TN 38105 USA

[9] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 36期

关键词：

HER2; breast cancer; bladder cancer; GROWTH-FACTOR RECEPTOR-3; BREAST-CANCER; ACTIVATING MUTATIONS; SOMATIC MUTATIONS; POINT MUTATION; NEU ONCOGENE; INHIBITOR; GEFITINIB; HER2; PROGRESSION;

D O I：

10.1073/pnas.1203201109

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：

We assessed somatic alleles of six receptor tyrosine kinase genes mutated in lung adenocarcinoma for oncogenic activity. Five of these genes failed to score in transformation assays; however, novel recurring extracellular domain mutations of the receptor tyrosine kinase gene ERBB2 were potently oncogenic. These ERBB2 extracellular domain mutants were activated by two distinct mechanisms, characterized by elevated C-terminal tail phosphorylation or by covalent dimerization mediated by intermolecular disulfide bond formation. These distinct mechanisms of receptor activation converged upon tyrosine phosphorylation of cellular proteins, impacting cell motility. Survival of Ba/F3 cells transformed to IL-3 independence by the ERBB2 extracellular domain mutants was abrogated by treatment with small-molecule inhibitors of ERBB2, raising the possibility that patients harboring such mutations could benefit from ERBB2-directed therapy.

引用

页码：14476 / 14481

页数：6

共 47 条

[1] Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop [J].

Aceto, Nicola ;

Sausgruber, Nina ;

Brinkhaus, Heike ;

Gaidatzis, Dimos ;

Martiny-Baron, Georg ;

Mazzarol, Giovanni ;

Confalonieri, Stefano ;

Quarto, Micaela ;

Hu, Guang ;

Balwierz, Piotr J. ;

Pachkov, Mikhail ;

Elledge, Stephen J. ;

van Nimwegen, Erik ;

Stadler, Michael B. ;

Bentires-Alj, Mohamed .

NATURE MEDICINE, 2012, 18 (04) :529-537

[2] Sequence analysis of mutations and translocations across breast cancer subtypes [J].

Banerji, Shantanu ;

Cibulskis, Kristian ;

Rangel-Escareno, Claudia ;

Brown, Kristin K. ;

Carter, Scott L. ;

Frederick, Abbie M. ;

Lawrence, Michael S. ;

Sivachenko, Andrey Y. ;

Sougnez, Carrie ;

Zou, Lihua ;

Cortes, Maria L. ;

Fernandez-Lopez, Juan C. ;

Peng, Shouyong ;

Ardlie, Kristin G. ;

Auclair, Daniel ;

Bautista-Pina, Veronica ;

Duke, Fujiko ;

Francis, Joshua ;

Jung, Joonil ;

Maffuz-Aziz, Antonio ;

Onofrio, Robert C. ;

Parkin, Melissa ;

Pho, Nam H. ;

Quintanar-Jurado, Valeria ;

Ramos, Alex H. ;

Rebollar-Vega, Rosa ;

Rodriguez-Cuevas, Sergio ;

Romero-Cordoba, Sandra L. ;

Schumacher, Steven E. ;

Stransky, Nicolas ;

Thompson, Kristin M. ;

Uribe-Figueroa, Laura ;

Baselga, Jose ;

Beroukhim, Rameen ;

Polyak, Kornelia ;

Sgroi, Dennis C. ;

Richardson, Andrea L. ;

Jimenez-Sanchez, Gerardo ;

Lander, Eric S. ;

Gabriel, Stacey B. ;

Garraway, Levi A. ;

Golub, Todd R. ;

Melendez-Zajgla, Jorge ;

Toker, Alex ;

Getz, Gad ;

Hidalgo-Miranda, Alfredo ;

Meyerson, Matthew .

NATURE, 2012, 486 (7403) :405-409

[3] MULTIPLE INDEPENDENT ACTIVATIONS OF THE NEU ONCOGENE BY A POINT MUTATION ALTERING THE TRANSMEMBRANE DOMAIN OF P185 [J].

BARGMANN, CI ;

HUNG, MC ;

WEINBERG, RA .

CELL, 1986, 45 (05) :649-657

[4] The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity [J].

Barretina, Jordi ;

Caponigro, Giordano ;

Stransky, Nicolas ;

Venkatesan, Kavitha ;

Margolin, Adam A. ;

Kim, Sungjoon ;

Wilson, Christopher J. ;

Lehar, Joseph ;

Kryukov, Gregory V. ;

Sonkin, Dmitriy ;

Reddy, Anupama ;

Liu, Manway ;

Murray, Lauren ;

Berger, Michael F. ;

Monahan, John E. ;

Morais, Paula ;

Meltzer, Jodi ;

Korejwa, Adam ;

Jane-Valbuena, Judit ;

Mapa, Felipa A. ;

Thibault, Joseph ;

Bric-Furlong, Eva ;

Raman, Pichai ;

Shipway, Aaron ;

Engels, Ingo H. ;

Cheng, Jill ;

Yu, Guoying K. ;

Yu, Jianjun ;

Aspesi, Peter, Jr. ;

de Silva, Melanie ;

Jagtap, Kalpana ;

Jones, Michael D. ;

Wang, Li ;

Hatton, Charles ;

Palescandolo, Emanuele ;

Gupta, Supriya ;

Mahan, Scott ;

Sougnez, Carrie ;

Onofrio, Robert C. ;

Liefeld, Ted ;

MacConaill, Laura ;

Winckler, Wendy ;

Reich, Michael ;

Li, Nanxin ;

Mesirov, Jill P. ;

Gabriel, Stacey B. ;

Getz, Gad ;

Ardlie, Kristin ;

Chan, Vivien ;

Myer, Vic E. .

NATURE, 2012, 483 (7391) :603-607

[5] Integrated genomic analyses of ovarian carcinoma [J].

Bell, D. ;

Berchuck, A. ;

Birrer, M. ;

Chien, J. ;

Cramer, D. W. ;

Dao, F. ;

Dhir, R. ;

DiSaia, P. ;

Gabra, H. ;

Glenn, P. ;

Godwin, A. K. ;

Gross, J. ;

Hartmann, L. ;

Huang, M. ;

Huntsman, D. G. ;

Iacocca, M. ;

Imielinski, M. ;

Kalloger, S. ;

Karlan, B. Y. ;

Levine, D. A. ;

Mills, G. B. ;

Morrison, C. ;

Mutch, D. ;

Olvera, N. ;

Orsulic, S. ;

Park, K. ;

Petrelli, N. ;

Rabeno, B. ;

Rader, J. S. ;

Sikic, B. I. ;

Smith-McCune, K. ;

Sood, A. K. ;

Bowtell, D. ;

Penny, R. ;

Testa, J. R. ;

Chang, K. ;

Dinh, H. H. ;

Drummond, J. A. ;

Fowler, G. ;

Gunaratne, P. ;

Hawes, A. C. ;

Kovar, C. L. ;

Lewis, L. R. ;

Morgan, M. B. ;

Newsham, I. F. ;

Santibanez, J. ;

Reid, J. G. ;

Trevino, L. R. ;

Wu, Y. -Q. ;

Wang, M. .

NATURE, 2011, 474 (7353) :609-615

[6] Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes [J].

Chen, Chun-Long ;

Rappailles, Aurelien ;

Duquenne, Lauranne ;

Huvet, Maxime ;

Guilbaud, Guillaume ;

Farinelli, Laurent ;

Audit, Benjamin ;

d'Aubenton-Carafa, Yves ;

Arneodo, Alain ;

Hyrien, Olivier ;

Thermes, Claude .

GENOME RESEARCH, 2010, 20 (04) :447-457

[7] Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma [J].

Chesi, M ;

Brents, LA ;

Fly, SA ;

Bais, C ;

Robbiani, DF ;

Mesri, E ;

Kuehl, WM ;

Bergsagel, PL .

BLOOD, 2001, 97 (03) :729-736

[8] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[9] Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab [J].

Cho, HS ;

Mason, K ;

Ramyar, KX ;

Stanley, AM ;

Gabelli, SB ;

Denney, DW ;

Leahy, DJ .

NATURE, 2003, 421 (6924) :756-760

[10]

d'Avis PY, 1998, CELL GROWTH DIFFER, V9, P71

← 1 2 3 4 5 →