Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 299 (5607): 708-710

Copyright © 2003 by the American Association for the Advancement of Science

PDGFRA Activating Mutations in Gastrointestinal Stromal Tumors

Michael C. Heinrich,1* Christopher L. Corless,2 Anette Duensing,3 Laura McGreevey,1 Chang-Jie Chen,3 Nora Joseph,3 Samuel Singer,4 Diana J. Griffith,1 Andrea Haley,1 Ajia Town,1 George D. Demetri,5 Christopher D. M. Fletcher,3 Jonathan A. Fletcher35*

Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits KIT kinase activity. Here we show that ~35% (14 of 40) of GISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor alpha  (PDGFRA). Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect to activation of downstream signaling intermediates and cytogenetic changes associated with tumor progression. Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs.

1 Department of Medicine,
2 Department of Pathology, Oregon Health & Science University Cancer Institute and Portland VA Medical Center, Portland, OR 97201, USA.
3 Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA, and Harvard Medical School, Boston, MA 02115, USA.
4 Department of Surgery, Memorial Sloan-Kettering Cancer Institute, New York, NY 10021, USA.
5 Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail: heinrich{at}ohsu.edu, jfletcher{at}partners.org



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Recent advances in the treatment of gastrointestinal stromal tumors.
C. Serrano and S. George (2014)
Therapeutic Advances in Medical Oncology 6, 115-127
   Abstract »    PDF »
Unbiased Compound Screening Identifies Unexpected Drug Sensitivities and Novel Treatment Options for Gastrointestinal Stromal Tumors.
S. Boichuk, D. J. Lee, K. R. Mehalek, K. R. Makielski, A. Wozniak, D. S. Seneviratne, N. Korzeniewski, R. Cuevas, J. A. Parry, M. F. Brown, et al. (2014)
Cancer Res. 74, 1200-1213
   Abstract »    Full Text »    PDF »
A Reactive Oxygen Species-Mediated, Self-Perpetuating Loop Persistently Activates Platelet-Derived Growth Factor Receptor {alpha}.
H. Lei and A. Kazlauskas (2014)
Mol. Cell. Biol. 34, 110-122
   Abstract »    Full Text »    PDF »
KIT oncogene inhibition drives intratumoral macrophage M2 polarization.
M. J. Cavnar, S. Zeng, T. S. Kim, E. C. Sorenson, L. M. Ocuin, V. P. Balachandran, A. M. Seifert, J. B. Greer, R. Popow, M. H. Crawley, et al. (2013)
J. Exp. Med. 210, 2873-2886
   Abstract »    Full Text »    PDF »
Sarcoma genomics.
R. Jones and D. Wood (2013)
Bone and Joint 360 2, 2-8
   Abstract »    Full Text »    PDF »
Optimizing Tyrosine Kinase Inhibitor Therapy in Gastrointestinal Stromal Tumors: Exploring the Benefits of Continuous Kinase Suppression.
A. Le Cesne, J.-Y. Blay, P. Reichardt, and H. Joensuu (2013)
Oncologist 18, 1192-1199
   Abstract »    Full Text »    PDF »
Pharmacokinetics, Clinical Indications, and Resistance Mechanisms in Molecular Targeted Therapies in Cancer.
B. Izar, J. Rotow, J. Gainor, J. Clark, and B. Chabner (2013)
Pharmacol. Rev. 65, 1351-1395
   Abstract »    Full Text »    PDF »
The DREAM Complex Mediates GIST Cell Quiescence and Is a Novel Therapeutic Target to Enhance Imatinib-Induced Apoptosis.
S. Boichuk, J. A. Parry, K. R. Makielski, L. Litovchick, J. L. Baron, J. P. Zewe, A. Wozniak, K. R. Mehalek, N. Korzeniewski, D. S. Seneviratne, et al. (2013)
Cancer Res. 73, 5120-5129
   Abstract »    Full Text »    PDF »
Structural and Functional Properties of Platelet-Derived Growth Factor and Stem Cell Factor Receptors.
C.-H. Heldin and J. Lennartsson (2013)
Cold Spring Harb Perspect Biol 5, a009100
   Abstract »    Full Text »    PDF »
Drug Repurposing for Gastrointestinal Stromal Tumor.
Z. Y. Pessetto, S. J. Weir, G. Sethi, M. A. Broward, and A. K. Godwin (2013)
Mol. Cancer Ther. 12, 1299-1309
   Abstract »    Full Text »    PDF »
DOG1 Regulates Growth and IGFBP5 in Gastrointestinal Stromal Tumors.
S. Simon, F. Grabellus, L. Ferrera, L. Galietta, B. Schwindenhammer, T. Muhlenberg, G. Taeger, G. Eilers, J. Treckmann, F. Breitenbuecher, et al. (2013)
Cancer Res. 73, 3661-3670
   Abstract »    Full Text »    PDF »
Immune Infiltrates Are Prognostic Factors in Localized Gastrointestinal Stromal Tumors.
S. Rusakiewicz, M. Semeraro, M. Sarabi, M. Desbois, C. Locher, R. Mendez, N. Vimond, A. Concha, F. Garrido, N. Isambert, et al. (2013)
Cancer Res. 73, 3499-3510
   Abstract »    Full Text »    PDF »
Genomics of Squamous Cell Lung Cancer.
M. Rooney, S. Devarakonda, and R. Govindan (2013)
Oncologist 18, 707-716
   Abstract »    Full Text »    PDF »
Mutational Analysis of Gastrointestinal Stromal Tumors (GISTs): Procedural Approach for Diagnostic Purposes.
R. PALMIROTTA, M. L. DE MARCHIS, G. LUDOVICI, B. LEONE, R. COVELLO, S. CONTI, L. COSTARELLI, D. DELLA-MORTE, P. FERRONI, M. ROSELLI, et al. (2013)
Cancer Genomics Proteomics 10, 115-123
   Abstract »    Full Text »    PDF »
Neurofibromatosis type-1 with retroperitoneal stromal tumour: one case report.
G.-q. Zong, Y. Fei, F. Wang, and R.-m. Liu (2013)
Scottish Medical Journal 58, e37-e40
   Abstract »    Full Text »    PDF »
Neoadjuvant Imatinib for Borderline Resectable GIST.
M. Z. Koontz, B. M. Visser, and P. L. Kunz (2012)
J Natl Compr Canc Netw 10, 1477-1482
   Abstract »    Full Text »    PDF »
Stromal Platelet-Derived Growth Factor Receptor {alpha} (PDGFR{alpha}) Provides a Therapeutic Target Independent of Tumor Cell PDGFR{alpha} Expression in Lung Cancer Xenografts.
D. E. Gerber, P. Gupta, M. T. Dellinger, J. E. Toombs, M. Peyton, I. Duignan, J. Malaby, T. Bailey, C. Burns, R. A. Brekken, et al. (2012)
Mol. Cancer Ther. 11, 2473-2482
   Abstract »    Full Text »    PDF »
Current and emerging strategies for the management of imatinib-refractory advanced gastrointestinal stromal tumors.
D. Kee and J. R. Zalcberg (2012)
Therapeutic Advances in Medical Oncology 4, 255-270
   Abstract »    PDF »
Rapid Relapse after Resection of a Sunitinib-resistant Gastrointestinal Stromal Tumor Harboring a Secondary Mutation in Exon 13 of the c-KIT Gene.
H. KIKUCHI, S. MIYAZAKI, T. SETOGUCHI, Y. HIRAMATSU, M. OHTA, K. KAMIYA, T. SAKAGUCHI, and H. KONNO (2012)
Anticancer Res 32, 4105-4109
   Abstract »    Full Text »    PDF »
Anti-tumor effects of the Notch pathway in gastrointestinal stromal tumors.
A. G. Dumont, Y. Yang, D. Reynoso, D. Katz, J. C. Trent, and D. P. Hughes (2012)
Carcinogenesis 33, 1674-1683
   Abstract »    Full Text »    PDF »
Imatinib resistance and microcytic erythrocytosis in a KitV558{Delta};T669I/+ gatekeeper-mutant mouse model of gastrointestinal stromal tumor.
B. Bosbach, S. Deshpande, F. Rossi, J.-H. Shieh, G. Sommer, E. de Stanchina, D. R. Veach, J. M. Scandura, K. Manova-Todorova, M. A. S. Moore, et al. (2012)
PNAS 109, E2276-E2283
   Abstract »    Full Text »    PDF »
Crenolanib Inhibits the Drug-Resistant PDGFRA D842V Mutation Associated with Imatinib-Resistant Gastrointestinal Stromal Tumors.
M. C. Heinrich, D. Griffith, A. McKinley, J. Patterson, A. Presnell, A. Ramachandran, and M. Debiec-Rychter (2012)
Clin. Cancer Res. 18, 4375-4384
   Abstract »    Full Text »    PDF »
Soft Tissue Sarcoma, Version 2.2012: Featured Updates to the NCCN Guidelines.
M. von Mehren, R. S. Benjamin, M. M. Bui, E. S. Casper, E. U. Conrad III, T. F. DeLaney, K. N. Ganjoo, S. George, R. Gonzalez, M. J. Heslin, et al. (2012)
J Natl Compr Canc Netw 10, 951-960
   Abstract »    Full Text »    PDF »
Complete Longitudinal Analyses of the Randomized, Placebo-Controlled, Phase III Trial of Sunitinib in Patients with Gastrointestinal Stromal Tumor following Imatinib Failure.
G. D. Demetri, C. R. Garrett, P. Schoffski, M. H. Shah, J. Verweij, S. Leyvraz, H. I. Hurwitz, A. L. Pousa, A. Le Cesne, D. Goldstein, et al. (2012)
Clin. Cancer Res. 18, 3170-3179
   Abstract »    Full Text »    PDF »
Gastric Antral Vascular Ectasia in a Patient with GIST after Treatment with Imatinib: Case Report and Literature Review.
E. Saad Aldin, F. Mourad, and A. Tfayli (2012)
Jpn. J. Clin. Oncol. 42, 447-450
   Abstract »    Full Text »    PDF »
A nonrandom association of gastrointestinal stromal tumor (GIST) and desmoid tumor (deep fibromatosis): case series of 28 patients.
A. G. Dumont, L. Rink, A. K. Godwin, M. Miettinen, H. Joensuu, J. R. Strosberg, A. Gronchi, C. L. Corless, D. Goldstein, B. P. Rubin, et al. (2012)
Ann. Onc. 23, 1335-1340
   Abstract »    Full Text »    PDF »
ACRIN 6665/RTOG 0132 Phase II Trial of Neoadjuvant Imatinib Mesylate for Operable Malignant Gastrointestinal Stromal Tumor: Monitoring with 18F-FDG PET and Correlation with Genotype and GLUT4 Expression.
A. D. Van den Abbeele, C. Gatsonis, D. J. de Vries, Y. Melenevsky, A. Szot-Barnes, J. T. Yap, A. K. Godwin, L. Rink, M. Huang, M. Blevins, et al. (2012)
J. Nucl. Med. 53, 567-574
   Abstract »    Full Text »    PDF »
KRAS and BRAF Mutations Predict Primary Resistance to Imatinib in Gastrointestinal Stromal Tumors.
C. Miranda, M. Nucifora, F. Molinari, E. Conca, M. C. Anania, A. Bordoni, P. Saletti, L. Mazzucchelli, S. Pilotti, M. A. Pierotti, et al. (2012)
Clin. Cancer Res. 18, 1769-1776
   Abstract »    Full Text »    PDF »
Clinical activity of sorafenib in patients with advanced gastrointestinal stromal tumor bearing PDGFRA exon 18 mutation: a case series.
G. Roubaud, M. Kind, J.- M. Coindre, R. G. Maki, B. Bui, and A. Italiano (2012)
Ann. Onc. 23, 804-805
   Full Text »    PDF »
Aberrant DNA methylation associated with aggressiveness of gastrointestinal stromal tumour.
Y. Okamoto, A. Sawaki, S. Ito, T. Nishida, T. Takahashi, M. Toyota, H. Suzuki, Y. Shinomura, I. Takeuchi, K. Shinjo, et al. (2012)
Gut 61, 392-401
   Abstract »    Full Text »    PDF »
Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience.
A. Wozniak, P. Rutkowski, A. Piskorz, M. Ciwoniuk, C. Osuch, E. Bylina, J. Sygut, M. Chosia, J. Rys, K. Urbanczyk, et al. (2012)
Ann. Onc. 23, 353-360
   Abstract »    Full Text »    PDF »
Mitotic Checkpoints and Chromosome Instability Are Strong Predictors of Clinical Outcome in Gastrointestinal Stromal Tumors.
P. Lagarde, G. Perot, A. Kauffmann, C. Brulard, V. Dapremont, I. Hostein, A. Neuville, A. Wozniak, R. Sciot, P. Schoffski, et al. (2012)
Clin. Cancer Res. 18, 826-838
   Abstract »    Full Text »    PDF »
MicroRNA-494 Downregulates KIT and Inhibits Gastrointestinal Stromal Tumor Cell Proliferation.
W. K. Kim, M. Park, Y.-K. Kim, Y. K. Tae, H.-K. Yang, J. M. Lee, and H. Kim (2011)
Clin. Cancer Res. 17, 7584-7594
   Abstract »    Full Text »    PDF »
Small-Intestinal Rhabdoid Gastrointestinal Stromal Tumor (GIST): Mutation Analysis and Clinical Implications of a Rare Morphological Variant.
J. A. Hanson, J. C. Trent, D. Yang, and K. Cooper (2011)
International Journal of Surgical Pathology 19, 653-657
   Abstract »    PDF »
Evaluation of Prognostic Factors and Their Capacity to Predict Biological Behavior in Gastrointestinal Stromal Tumors.
S. Calabuig-Farinas, J. A. Lopez-Guerrero, S. Navarro, I. Machado, A. Poveda, A. Pellin, and A. Llombart-Bosch (2011)
International Journal of Surgical Pathology 19, 448-461
   Abstract »    PDF »
Added value of molecular targeted agents in oncology.
J.- C. Soria, J. Y. Blay, J. P. Spano, X. Pivot, Y. Coscas, and D. Khayat (2011)
Ann. Onc. 22, 1703-1716
   Abstract »    Full Text »    PDF »
Pathological Signaling via Platelet-Derived Growth Factor Receptor {alpha} Involves Chronic Activation of Akt and Suppression of p53.
H. Lei, G. Velez, and A. Kazlauskas (2011)
Mol. Cell. Biol. 31, 1788-1799
   Abstract »    Full Text »    PDF »
PDGF induced microRNA alterations in cancer cells.
M. Shao, S. Rossi, B. Chelladurai, M. Shimizu, O. Ntukogu, M. Ivan, G. A. Calin, and D. Matei (2011)
Nucleic Acids Res. 39, 4035-4047
   Abstract »    Full Text »    PDF »
Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease.
C. Elling, P. Erben, C. Walz, M. Frickenhaus, M. Schemionek, M. Stehling, H. Serve, N. C. P. Cross, A. Hochhaus, W.-K. Hofmann, et al. (2011)
Blood 117, 2935-2943
   Abstract »    Full Text »    PDF »
Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations.
K. A. Janeway, S. Y. Kim, M. Lodish, V. Nose, P. Rustin, J. Gaal, P. L. M. Dahia, B. Liegl, E. R. Ball, M. Raygada, et al. (2011)
PNAS 108, 314-318
   Abstract »    Full Text »    PDF »
Clinical Efficacy and Safety of Sunitinib After Imatinib Failure in Japanese Patients with Gastrointestinal Stromal Tumor.
K. Matsumoto, A. Sawaki, N. Mizuno, K. Hara, S. Hijioka, Y. Niwa, M. Tajika, H. Kawai, S. Kondo, and K. Yamao (2011)
Jpn. J. Clin. Oncol. 41, 57-62
   Abstract »    Full Text »    PDF »
New insights into the mechanisms of hematopoietic cell transformation by activated receptor tyrosine kinases.
F. Toffalini and J.-B. Demoulin (2010)
Blood 116, 2429-2437
   Abstract »    Full Text »    PDF »
A phase I-II study of everolimus (RAD001) in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors.
P. Schoffski, P. Reichardt, J.- Y. Blay, H. Dumez, J. A. Morgan, I. Ray-Coquard, N. Hollaender, A. Jappe, and G. D. Demetri (2010)
Ann. Onc. 21, 1990-1998
   Abstract »    Full Text »    PDF »
Soft tissue sarcoma: from molecular diagnosis to selection of treatment. Pathological diagnosis of soft tissue sarcoma amid molecular biology and targeted therapies.
E. Wardelmann, H.- U. Schildhaus, S. Merkelbach-Bruse, W. Hartmann, P. Reichardt, P. Hohenberger, and R. Buttner (2010)
Ann. Onc. 21, vii265-vii269
   Abstract »    Full Text »    PDF »
Coactivated Platelet-Derived Growth Factor Receptor {alpha} and Epidermal Growth Factor Receptor Are Potential Therapeutic Targets in Intimal Sarcoma.
B. Dewaele, G. Floris, J. Finalet-Ferreiro, C. D. Fletcher, J.-M. Coindre, L. Guillou, P. C. W. Hogendoorn, A. Wozniak, V. Vanspauwen, P. Schoffski, et al. (2010)
Cancer Res. 70, 7304-7314
   Abstract »    Full Text »    PDF »
ZIC1 Overexpression Is Oncogenic in Liposarcoma.
E. Brill, R. Gobble, C. Angeles, M. Lagos-Quintana, A. Crago, B. Laxa, P. DeCarolis, L. Zhang, C. Antonescu, N. D. Socci, et al. (2010)
Cancer Res. 70, 6891-6901
   Abstract »    Full Text »    PDF »
Pediatric mastocytosis-associated KIT extracellular domain mutations exhibit different functional and signaling properties compared with KIT-phosphotransferase domain mutations.
Y. Yang, S. Letard, L. Borge, A. Chaix, K. Hanssens, S. Lopez, M. Vita, P. Finetti, D. Birnbaum, F. Bertucci, et al. (2010)
Blood 116, 1114-1123
   Abstract »    Full Text »    PDF »
Clinical characteristics and surgical treatment of oesophageal gastrointestinal stromal tumours.
P. Jiang, Z. Jiao, B. Han, X. Zhang, X. Sun, J. Su, C. Wang, and B. Gao (2010)
Eur J Cardiothorac Surg 38, 223-227
   Abstract »    Full Text »    PDF »
Soft Tissue Sarcoma.
G. D. Demetri, S. Antonia, R. S. Benjamin, M. M. Bui, E. S. Casper, E. U. Conrad III, T. F. DeLaney, K. N. Ganjoo, M. J. Heslin, R. J. Hutchinson, et al. (2010)
J Natl Compr Canc Netw 8, 630-674
   Full Text »    PDF »
NCCN Task Force Report: Update on the Management of Patients with Gastrointestinal Stromal Tumors.
G. D. Demetri, M. von Mehren, C. R. Antonescu, R. P. DeMatteo, K. N. Ganjoo, R. G. Maki, P. W. T. Pisters, C. P. Raut, R. F. Riedel, S. Schuetze, et al. (2010)
J Natl Compr Canc Netw 8, S-1-S-41
   Abstract »    Full Text »    PDF »
Autocrine IGF-1/IGF-1R signaling is responsible for constitutive PI3K/Akt activation in acute myeloid leukemia: therapeutic value of neutralizing anti-IGF-1R antibody.
N. Chapuis, J. Tamburini, P. Cornillet-Lefebvre, L. Gillot, V. Bardet, L. Willems, S. Park, A. S Green, N. Ifrah, F. Dreyfus, et al. (2010)
Haematologica 95, 415-423
   Abstract »    Full Text »    PDF »
Selective recruitment of breast cancer anti-estrogen resistance genes and relevance for breast cancer progression and tamoxifen therapy response.
T. van Agthoven, A. M Sieuwerts, D. Meijer, M. E Meijer-van Gelder, T. L A van Agthoven, R. Sarwari, S. Sleijfer, J. A Foekens, and L. C J Dorssers (2010)
Endocr. Relat. Cancer 17, 215-230
   Abstract »    Full Text »    PDF »
Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients?.
C. Mussi, U. Ronellenfitsch, J. Jakob, E. Tamborini, P. Reichardt, P. G. Casali, M. Fiore, P. Hohenberger, and A. Gronchi (2010)
Ann. Onc. 21, 403-408
   Abstract »    Full Text »    PDF »
Pharmacological management of gastrointestinal stromal tumours: an update on the role of sunitinib.
J.-Y. Blay (2010)
Ann. Onc. 21, 208-215
   Abstract »    Full Text »    PDF »
BRAF Mutation Status in Gastrointestinal Stromal Tumors.
I. Hostein, N. Faur, C. Primois, F. Boury, J. Denard, J.-F. Emile, P.-P. Bringuier, J.-Y. Scoazec, and J.-M. Coindre (2010)
Am J Clin Pathol 133, 141-148
   Abstract »    Full Text »    PDF »
Proapoptotic Activity of Bortezomib in Gastrointestinal Stromal Tumor Cells.
S. Bauer, J. A. Parry, T. Muhlenberg, M. F. Brown, D. Seneviratne, P. Chatterjee, A. Chin, B. P. Rubin, S.-F. Kuan, J. A. Fletcher, et al. (2010)
Cancer Res. 70, 150-159
   Abstract »    Full Text »    PDF »
Resistance to Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors.
A. W. Gramza, C. L. Corless, and M. C. Heinrich (2009)
Clin. Cancer Res. 15, 7510-7518
   Abstract »    Full Text »    PDF »
Personalized Cancer Therapy With Selective Kinase Inhibitors: An Emerging Paradigm in Medical Oncology.
U. McDermott and J. Settleman (2009)
J. Clin. Oncol. 27, 5650-5659
   Abstract »    Full Text »    PDF »
Mechanisms of Sunitinib Resistance in Gastrointestinal Stromal Tumors Harboring KITAY502-3ins Mutation: An In vitro Mutagenesis Screen for Drug Resistance.
T. Guo, M. Hajdu, N. P. Agaram, H. Shinoda, D. Veach, B. D. Clarkson, R. G. Maki, S. Singer, R. P. DeMatteo, P. Besmer, et al. (2009)
Clin. Cancer Res. 15, 6862-6870
   Abstract »    Full Text »    PDF »
Expression and Mutational Status of PDGFR in Thymic Tumours.
M. MEISTER, P. KAHL, T. MULEY, A. MORRESI-HAUF, C. SEBENING, M. A. KERN, M. BREINIG, P. SCHNABEL, H. DIENEMANN, P. SCHIRMACHER, et al. (2009)
Anticancer Res 29, 4057-4061
   Abstract »    Full Text »    PDF »
Adjuvant Chemotherapy in Localized Soft Tissue Sarcomas: Still Not Proven.
J.-Y. Blay and A. Le Cesne (2009)
Oncologist 14, 1013-1020
   Abstract »    Full Text »    PDF »
Molecular Target Modulation, Imaging, and Clinical Evaluation of Gastrointestinal Stromal Tumor Patients Treated with Sunitinib Malate after Imatinib Failure.
G. D. Demetri, M. C. Heinrich, J. A. Fletcher, C. D.M. Fletcher, A. D. Van den Abbeele, C. L. Corless, C. R. Antonescu, S. George, J. A. Morgan, M. H. Chen, et al. (2009)
Clin. Cancer Res. 15, 5902-5909
   Abstract »    Full Text »    PDF »
Inhibitors of Deacetylases Suppress Oncogenic KIT Signaling, Acetylate HSP90, and Induce Apoptosis in Gastrointestinal Stromal Tumors.
T. Muhlenberg, Y. Zhang, A. J. Wagner, F. Grabellus, J. Bradner, G. Taeger, H. Lang, T. Taguchi, M. Schuler, J. A. Fletcher, et al. (2009)
Cancer Res. 69, 6941-6950
   Abstract »    Full Text »    PDF »
Growth Factors Outside the PDGF Family Drive Experimental PVR.
H. Lei, G. Velez, P. Hovland, T. Hirose, D. Gilbertson, and A. Kazlauskas (2009)
Invest. Ophthalmol. Vis. Sci. 50, 3394-3403
   Abstract »    Full Text »    PDF »
Cell Cycle/Apoptosis Molecule Expression Correlates with Imatinib Response in Patients with Advanced Gastrointestinal Stromal Tumors.
S. Romeo, M. Debiec-Rychter, M. Van Glabbeke, H. Van Paassen, P. Comite, R. Van Eijk, J. Oosting, J. Verweij, P. Terrier, U. Schneider, et al. (2009)
Clin. Cancer Res. 15, 4191-4198
   Abstract »    Full Text »    PDF »
Successes and Challenges in Translational Research: The Development of Targeted Therapy for Gastrointestinal Stromal Tumours.
D. J. Renouf, L. Wilson, and C. D. Blanke (2009)
Clin. Cancer Res. 15, 3908-3911
   Abstract »    Full Text »    PDF »
Ligand-Dependent Platelet-Derived Growth Factor Receptor (PDGFR)-{alpha} Activation Sensitizes Rare Lung Cancer and Sarcoma Cells to PDGFR Kinase Inhibitors.
U. McDermott, R. Y. Ames, A. J. Iafrate, S. Maheswaran, H. Stubbs, P. Greninger, K. McCutcheon, R. Milano, A. Tam, D. Y. Lee, et al. (2009)
Cancer Res. 69, 3937-3946
   Abstract »    Full Text »    PDF »
Identification of Smyd4 as a Potential Tumor Suppressor Gene Involved in Breast Cancer Development.
L. Hu, Y. T. Zhu, C. Qi, and Y.-J. Zhu (2009)
Cancer Res. 69, 4067-4072
   Abstract »    Full Text »    PDF »
FIP1L1-PDGFR{alpha} Imposes Eosinophil Lineage Commitment on Hematopoietic Stem/Progenitor Cells.
K. Fukushima, I. Matsumura, S. Ezoe, M. Tokunaga, M. Yasumi, Y. Satoh, H. Shibayama, H. Tanaka, A. Iwama, and Y. Kanakura (2009)
J. Biol. Chem. 284, 7719-7732
   Abstract »    Full Text »    PDF »
Sustained Platelet-Derived Growth Factor Receptor {alpha} Signaling in Osteoblasts Results in Craniosynostosis by Overactivating the Phospholipase C-{gamma} Pathway.
A. Moenning, R. Jager, A. Egert, W. Kress, E. Wardelmann, and H. Schorle (2009)
Mol. Cell. Biol. 29, 881-891
   Abstract »    Full Text »    PDF »
Dose Escalation of Imatinib After Failure of Standard Dose in Korean Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumor.
I. Park, M.-H. Ryu, S. J. Sym, S. S. Lee, G. Jang, T. W. Kim, H. M. Chang, J.-L. Lee, H. Lee, and Y.-K. Kang (2009)
Jpn. J. Clin. Oncol. 39, 105-110
   Abstract »    Full Text »    PDF »
Approval Summary: Imatinib Mesylate in the Treatment of Metastatic and/or Unresectable Malignant Gastrointestinal Stromal Tumors.
M. H. Cohen, A. Farrell, R. Justice, and R. Pazdur (2009)
Oncologist 14, 174-180
   Abstract »    Full Text »    PDF »
Sorafenib induces growth suppression in mouse models of gastrointestinal stromal tumor.
H. Huynh, J. W.J. Lee, P. K.H. Chow, V. C. Ngo, G. B. Lew, I. W.L. Lam, H. S. Ong, A. Chung, and K. C. Soo (2009)
Mol. Cancer Ther. 8, 152-159
   Abstract »    Full Text »    PDF »
Primary and Secondary Kinase Genotypes Correlate With the Biological and Clinical Activity of Sunitinib in Imatinib-Resistant Gastrointestinal Stromal Tumor.
M. C. Heinrich, R. G. Maki, C. L. Corless, C. R. Antonescu, A. Harlow, D. Griffith, A. Town, A. Mckinley, W.-B. Ou, J. A. Fletcher, et al. (2008)
J. Clin. Oncol. 26, 5352-5359
   Abstract »    Full Text »    PDF »
Correlation of Kinase Genotype and Clinical Outcome in the North American Intergroup Phase III Trial of Imatinib Mesylate for Treatment of Advanced Gastrointestinal Stromal Tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group.
M. C. Heinrich, K. Owzar, C. L. Corless, D. Hollis, E. C. Borden, C. D.M. Fletcher, C. W. Ryan, M. von Mehren, C. D. Blanke, C. Rankin, et al. (2008)
J. Clin. Oncol. 26, 5360-5367
   Abstract »    Full Text »    PDF »
Prognosis, Imatinib Dose, and Benefit of Sunitinib in GIST: Knowing the Genotype.
I. R. Judson (2008)
J. Clin. Oncol. 26, 5322-5325
   Full Text »    PDF »
Imatinib Mesylate Induces Quiescence in Gastrointestinal Stromal Tumor Cells through the CDH1-SKP2-p27Kip1 Signaling Axis.
Y. Liu, S. A. Perdreau, P. Chatterjee, L. Wang, S.-F. Kuan, and A. Duensing (2008)
Cancer Res. 68, 9015-9023
   Abstract »    Full Text »    PDF »
Plexiform angiomyxoid myofibroblastic tumour: differential diagnosis of gastrointestinal stromal tumour in the stomach.
T T Rau, A Hartmann, W Dietmaier, J Schmitz, W Hohenberger, F Hofstaedter, and K Katenkamp (2008)
J. Clin. Pathol. 61, 1136-1137
   Abstract »    Full Text »    PDF »
Activity of Dasatinib, a Dual SRC/ABL Kinase Inhibitor, and IPI-504, a Heat Shock Protein 90 Inhibitor, against Gastrointestinal Stromal Tumor-Associated PDGFRAD842V Mutation.
B. Dewaele, B. Wasag, J. Cools, R. Sciot, H. Prenen, P. Vandenberghe, A. Wozniak, P. Schoffski, P. Marynen, and M. Debiec-Rychter (2008)
Clin. Cancer Res. 14, 5749-5758
   Abstract »    Full Text »    PDF »
Multiple Primary Sporadic Gastrointestinal Stromal Tumors in the Adult: An Underestimated Entity.
D. Gasparotto, S. Rossi, I. Bearzi, C. Doglioni, A. Marzotto, J. L. Hornick, A. Grizzo, C. Sartor, A. Mandolesi, R. Sciot, et al. (2008)
Clin. Cancer Res. 14, 5715-5721
   Abstract »    Full Text »    PDF »
FIP1L1/PDGFR{alpha} synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome.
Y. Yamada, A. Sanchez-Aguilera, E. B. Brandt, M. McBride, N. J. H. Al-Moamen, F. D. Finkelman, D. A. Williams, J. A. Cancelas, and M. E. Rothenberg (2008)
Blood 112, 2500-2507
   Abstract »    Full Text »    PDF »
Distinct Gene Expression-Defined Classes of Gastrointestinal Stromal Tumor.
U. Yamaguchi, R. Nakayama, K. Honda, H. Ichikawa, T. Hasegawa, M. Shitashige, M. Ono, A. Shoji, T. Sakuma, H. Kuwabara, et al. (2008)
J. Clin. Oncol. 26, 4100-4108
   Abstract »    Full Text »    PDF »
Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells.
W. F. Tam, T.-L. Gu, J. Chen, B. H. Lee, L. Bullinger, S. Frohling, A. Wang, S. Monti, T. R. Golub, and D. G. Gilliland (2008)
Blood 112, 1981-1992
   Abstract »    Full Text »    PDF »
Insulin-like growth factor (IGF) 1 and 2 help to predict disease outcome in GIST patients.
C. Braconi, R. Bracci, I. Bearzi, F. Bianchi, S. Sabato, A. Mandolesi, L. Belvederesi, S. Cascinu, N. Valeri, and R. Cellerino (2008)
Ann. Onc. 19, 1293-1298
   Abstract »    Full Text »    PDF »
Characteristics of KIT-negative gastrointestinal stromal tumours and diagnostic utility of protein kinase C theta immunostaining.
H E Lee, M A Kim, H S Lee, B L Lee, and W H Kim (2008)
J. Clin. Pathol. 61, 722-729
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882