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.
PDGFRA Activating Mutations in Gastrointestinal Stromal Tumors
Michael C. Heinrich,1*Christopher L. Corless,2Anette Duensing,3Laura McGreevey,1Chang-Jie Chen,3Nora Joseph,3Samuel Singer,4Diana J. Griffith,1Andrea Haley,1Ajia Town,1George D. Demetri,5Christopher D. M. Fletcher,3Jonathan A. Fletcher35*
Most gastrointestinal stromal tumors (GISTs) have activating
mutations in the KIT receptor tyrosine kinase, and most patientswith
GISTs respond well to Gleevec, which inhibits KIT kinaseactivity. Here
we show that ~35% (14 of 40) of GISTs lacking KITmutations have intragenic activation mutations in the relatedreceptor
tyrosine kinase, platelet-derived growth factor receptor (PDGFRA). Tumors expressing KIT or PDGFRA oncoproteins wereindistinguishable with respect to activation of downstream signalingintermediates and cytogenetic changes associated with tumor
progression.Thus, KIT and PDGFRA mutations
appear to be alternative and mutuallyexclusive 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
The editors suggest the following Related Resources on Science sites:
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.
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 »
Role of Platelet-Derived Growth Factors in the Testis.
S. Basciani, S. Mariani, G. Spera, and L. Gnessi (2010)
Endocr. Rev.
31, 916-939
|Abstract »|Full Text »|PDF »
New insights into the mechanisms of hematopoietic cell transformation by activated receptor tyrosine kinases.
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.
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.
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 »
Carney Triad: A Syndrome Featuring Paraganglionic, Adrenocortical, and Possibly Other Endocrine Tumors.
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.
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.
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 »
Role of platelet-derived growth factors in physiology and medicine.
Phase II, Open-Label Study Evaluating the Activity of Imatinib in Treating Life-Threatening Malignancies Known to Be Associated with Imatinib-Sensitive Tyrosine Kinases.
M. C. Heinrich, H. Joensuu, G. D. Demetri, C. L. Corless, J. Apperley, J. A. Fletcher, D. Soulieres, S. Dirnhofer, A. Harlow, A. Town, et al. (2008)
Clin. Cancer Res.
14, 2717-2725
|Abstract »|Full Text »|PDF »
KIT Mutations Induce Intracellular Retention and Activation of an Immature Form of the KIT Protein in Gastrointestinal Stromal Tumors.
S. Tabone-Eglinger, F. Subra, H. El Sayadi, L. Alberti, E. Tabone, J.-P. Michot, N. Theou-Anton, A. Lemoine, J.-Y. Blay, and J.-F. Emile (2008)
Clin. Cancer Res.
14, 2285-2294
|Abstract »|Full Text »|PDF »
Molecular alterations of KIT and PDGFRA in GISTs: evaluation of a Portuguese series.
A L Gomes, A Gouveia, A F Capelinha, D de la Cruz, P Silva, R M Reis, A Pimenta, and J M Lopes (2008)
J. Clin. Pathol.
61, 203-208
|Abstract »|Full Text »|PDF »
Oncogene addiction: setting the stage for molecularly targeted cancer therapy.
Monitoring Interactions between Receptor Tyrosine Kinases and Their Downstream Effector Proteins in Living Cells Using Bioluminescence Resonance Energy Transfer.
P. K. Tan, J. Wang, P.-L. H. Littler, K. K. Wong, T. A. Sweetnam, W. Keefe, N. R. Nash, E. C. Reding, F. Piu, M. R. Brann, et al. (2007)
Mol. Pharmacol.
72, 1440-1446
|Abstract »|Full Text »|PDF »
Association of Intratumoral Vascular Endothelial Growth Factor Expression and Clinical Outcome for Patients with Gastrointestinal Stromal Tumors Treated with Imatinib Mesylate.
J. C. McAuliffe, A. J.F. Lazar, D. Yang, D. M. Steinert, W. Qiao, P. F. Thall, A. K. Raymond, R. S. Benjamin, and J. C. Trent (2007)
Clin. Cancer Res.
13, 6727-6734
|Abstract »|Full Text »|PDF »
Pediatric KIT Wild-Type and Platelet-Derived Growth Factor Receptor {alpha} Wild-Type Gastrointestinal Stromal Tumors Share KIT Activation but not Mechanisms of Genetic Progression with Adult Gastrointestinal Stromal Tumors.
K. A. Janeway, B. Liegl, A. Harlow, C. Le, A. Perez-Atayde, H. Kozakewich, C. L. Corless, M. C. Heinrich, and J. A. Fletcher (2007)
Cancer Res.
67, 9084-9088
|Abstract »|Full Text »|PDF »
Platelet-Derived Growth Factor Receptor-{beta} Constitutive Activity Promotes Angiogenesis In Vivo and In Vitro.
P. U. Magnusson, C. Looman, A. Ahgren, Y. Wu, L. Claesson-Welsh, and R. L. Heuchel (2007)
Arterioscler Thromb Vasc Biol
27, 2142-2149
|Abstract »|Full Text »|PDF »
Clonal Evolution of Resistance to Imatinib in Patients with Metastatic Gastrointestinal Stromal Tumors.
J. Desai, S. Shankar, M. C. Heinrich, J. A. Fletcher, C. D. Fletcher, J. Manola, J. A. Morgan, C. L. Corless, S. George, K. Tuncali, et al. (2007)
Clin. Cancer Res.
13, 5398-5405
|Abstract »|Full Text »|PDF »
Multiple Gastrointestinal Stromal and Other Tumors Caused by Platelet-Derived Growth Factor Receptor {alpha} Gene Mutations: A Case Associated with a Germline V561D Defect.
B. Pasini, L. Matyakhina, T. Bei, M. Muchow, S. Boikos, B. Ferrando, J. A. Carney, and C. A. Stratakis (2007)
J. Clin. Endocrinol. Metab.
92, 3728-3732
|Abstract »|Full Text »|PDF »
Sorafenib Inhibits the Imatinib-Resistant KITT670I Gatekeeper Mutation in Gastrointestinal Stromal Tumor.
T. Guo, N. P. Agaram, G. C. Wong, G. Hom, D. D'Adamo, R. G. Maki, G. K. Schwartz, D. Veach, B. D. Clarkson, S. Singer, et al. (2007)
Clin. Cancer Res.
13, 4874-4881
|Abstract »|Full Text »|PDF »
(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.
