Cancer Research Cell Death Mechanisms and Cancer Therapy Protein Translation and Cancer
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Allander, S. V.
Right arrow Articles by Meltzer, P. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Allander, S. V.
Right arrow Articles by Meltzer, P. S.
[Cancer Research 61, 8624-8628, December 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Gastrointestinal Stromal Tumors with KIT Mutations Exhibit a Remarkably Homogeneous Gene Expression Profile1

Susanne V. Allander, Nina N. Nupponen, Markus Ringnér, Galen Hostetter, Greg W. Maher, Natalie Goldberger, Yidong Chen, John Carpten, Abdel G. Elkahloun and Paul S. Meltzer2

Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract, are believed to arise from the interstitial cells of Cajal. GISTs are characterized by mutations in the proto-oncogene KIT that lead to constitutive activation of its tyrosine kinase activity. The tyrosine kinase inhibitor STI571, active against the BCR-ABL fusion protein in chronic myeloid leukemia, was recently shown to be highly effective in GISTs. We used 13,826-element cDNA microarrays to define the expression patterns of 13 KIT mutation-positive GISTs and compared them with the expression profiles of a group of spindle cell tumors from locations outside the gastrointestinal tract. Our results showed a remarkably distinct and uniform expression profile for all of the GISTs. In particular, hierarchical clustering of a subset of 113 cDNAs placed all of the GIST samples into one branch, with a Pearson correlation >0.91. This homogeneity suggests that the molecular pathogenesis of a GIST results from expansion of a clone that has acquired an activating mutation in KIT without the extreme genetic instability found in the common epithelial cancers. The results provide insight into the histogenesis of GIST and the clinical behavior of this therapeutically responsive tumor.




This article has been cited by other articles:


Home page
 JCOHome page
U. Yamaguchi, R. Nakayama, K. Honda, H. Ichikawa, T. Hasegawa, M. Shitashige, M. Ono, A. Shoji, T. Sakuma, H. Kuwabara, et al.
Distinct Gene Expression-Defined Classes of Gastrointestinal Stromal Tumor
J. Clin. Oncol., September 1, 2008; 26(25): 4100 - 4108.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
F. Vogt, A. Zernecke, M. Beckner, N. Krott, A.-K. Bosserhoff, R. Hoffmann, M. A.M.J. Zandvoort, T. Jahnke, M. Kelm, C. Weber, et al.
Blockade of Angio-Associated Migratory Cell Protein Inhibits Smooth Muscle Cell Migration and Neointima Formation in Accelerated Atherosclerosis
J. Am. Coll. Cardiol., July 22, 2008; 52(4): 302 - 311.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
H E Lee, M A Kim, H S Lee, B L Lee, and W H Kim
Characteristics of KIT-negative gastrointestinal stromal tumours and diagnostic utility of protein kinase C theta immunostaining
J. Clin. Pathol., June 1, 2008; 61(6): 722 - 729.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Hase, T. Yokomizo, T. Shimizu, and M. Nakamura
Characterization of an Orphan G Protein-coupled Receptor, GPR20, That Constitutively Activates Gi Proteins
J. Biol. Chem., May 9, 2008; 283(19): 12747 - 12755.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
E. Thouennon, A. G. Elkahloun, J. Guillemot, A.-P. Gimenez-Roqueplo, J. Bertherat, A. Pierre, H. Ghzili, L. Grumolato, M. Muresan, M. Klein, et al.
Identification of Potential Gene Markers and Insights into the Pathophysiology of Pheochromocytoma Malignancy
J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4865 - 4872.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
L. Bozulic, P. J. Morin, T. Hunter, and B. A. Hemmings
Meeting Report: Targeting the Kinome--20 Years of Tyrosine Kinase Inhibitor Research in Basel
Sci. Signal., February 20, 2007; 2007(374): pe8 - pe8.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
L Tornillo and L M Terracciano
An update on molecular genetics of gastrointestinal stromal tumours.
J. Clin. Pathol., June 1, 2006; 59(6): 557 - 563.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Baird, S. Davis, C. R. Antonescu, U. L. Harper, R. L. Walker, Y. Chen, A. A. Glatfelter, P. H. Duray, and P. S. Meltzer
Gene Expression Profiling of Human Sarcomas: Insights into Sarcoma Biology
Cancer Res., October 15, 2005; 65(20): 9226 - 9235.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
G Eisenhofer, T-T Huynh, K Pacak, F M Brouwers, M M Walther, W M Linehan, P J Munson, M Mannelli, D S Goldstein, and A G Elkahloun
Distinct gene expression profiles in norepinephrine- and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel-Lindau syndrome
Endocr. Relat. Cancer, December 1, 2004; 11(4): 897 - 911.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. L. Corless, J. A. Fletcher, and M. C. Heinrich
Biology of Gastrointestinal Stromal Tumors
J. Clin. Oncol., September 15, 2004; 22(18): 3813 - 3825.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. L. Chen, J. C. Trent, E. F. Wu, G. N. Fuller, L. Ramdas, W. Zhang, A. K. Raymond, V. G. Prieto, C. O. Oyedeji, K. K. Hunt, et al.
A Missense Mutation in KIT Kinase Domain 1 Correlates with Imatinib Resistance in Gastrointestinal Stromal Tumors
Cancer Res., September 1, 2004; 64(17): 5913 - 5919.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Duensing, N. E. Joseph, F. Medeiros, F. Smith, J. L. Hornick, M. C. Heinrich, C. L. Corless, G. D. Demetri, C. D. M. Fletcher, and J. A. Fletcher
Protein Kinase C {theta} (PKC{theta}) Expression and Constitutive Activation in Gastrointestinal Stromal Tumors (GISTs)
Cancer Res., August 1, 2004; 64(15): 5127 - 5131.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
C. All-Ericsson, L. Girnita, A. Muller-Brunotte, B. Brodin, S. Seregard, A. Ostman, and O. Larsson
c-Kit-Dependent Growth of Uveal Melanoma Cells: A Potential Therapeutic Target?
Invest. Ophthalmol. Vis. Sci., July 1, 2004; 45(7): 2075 - 2082.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
R. B. West, C. L. Corless, X. Chen, B. P. Rubin, S. Subramanian, K. Montgomery, S. Zhu, C. A. Ball, T. O. Nielsen, R. Patel, et al.
The Novel Marker, DOG1, Is Expressed Ubiquitously in Gastrointestinal Stromal Tumors Irrespective of KIT or PDGFRA Mutation Status
Am. J. Pathol., July 1, 2004; 165(1): 107 - 113.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
P. Strobel, M. Hartmann, A. Jakob, K. Mikesch, I. Brink, S. Dirnhofer, and A. Marx
Thymic Carcinoma with Overexpression of Mutated KIT and the Response to Imatinib
N. Engl. J. Med., June 17, 2004; 350(25): 2625 - 2626.
[Full Text] [PDF]

Home page
 Genome ResHome page
H. K. Lee, A. K. Hsu, J. Sajdak, J. Qin, and P. Pavlidis
Coexpression Analysis of Human Genes Across Many Microarray Data Sets
Genome Res., June 1, 2004; 14(6): 1085 - 1094.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
C. L. Sawyers
Opportunities and challenges in the development of kinase inhibitor therapy for cancer
Genes & Dev., December 15, 2003; 17(24): 2998 - 3010.
[Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. C. Linn, R. B. West, J. R. Pollack, S. Zhu, T. Hernandez-Boussard, T. O. Nielsen, B. P. Rubin, R. Patel, J. R. Goldblum, D. Siegmund, et al.
Gene Expression Patterns and Gene Copy Number Changes in Dermatofibrosarcoma Protuberans
Am. J. Pathol., December 1, 2003; 163(6): 2383 - 2395.
[Abstract] [Full Text]

Home page
 Molecular Cancer TherapeuticsHome page
A. Frolov, S. Chahwan, M. Ochs, J. P. Arnoletti, Z.-Z. Pan, O. Favorova, J. Fletcher, M. von Mehren, B. Eisenberg, and A. K. Godwin
Response Markers and the Molecular Mechanisms of Action of Gleevec in Gastrointestinal Stromal Tumors
Mol. Cancer Ther., August 1, 2003; 2(8): 699 - 709.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
N. H. Segal, P. Pavlidis, C. R. Antonescu, R. G. Maki, W. S. Noble, D. DeSantis, J. M. Woodruff, J. J. Lewis, M. F. Brennan, A. N. Houghton, et al.
Classification and Subtype Prediction of Adult Soft Tissue Sarcoma by Functional Genomics
Am. J. Pathol., August 1, 2003; 163(2): 691 - 700.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. Komdeur, H. J. Hoekstra, W. M. Molenaar, E. van den Berg, N. Zwart, E. Pras, I. Plaza-Menacho, R. M. W. Hofstra, and W. T. A. van der Graaf
Clinicopathologic Assessment of Postradiation Sarcomas: KIT as a Potential Treatment Target
Clin. Cancer Res., August 1, 2003; 9(8): 2926 - 2932.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
U. R. Kees, J. Ford, M. Watson, A. Murch, M. Ringner, R. L. Walker, and P. Meltzer
Gene Expression Profiles in a Panel of Childhood Leukemia Cell Lines Mirror Critical Features of the Disease
Mol. Cancer Ther., July 1, 2003; 2(7): 671 - 677.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. Grumolato, A. G. Elkahloun, H. Ghzili, D. Alexandre, C. Coulouarn, L. Yon, J.-P. Salier, L. E. Eiden, A. Fournier, H. Vaudry, et al.
Microarray and Suppression Subtractive Hybridization Analyses of Gene Expression in Pheochromocytoma Cells Reveal Pleiotropic Effects of Pituitary Adenylate Cyclase-Activating Polypeptide on Cell Proliferation, Survival, and Adhesion
Endocrinology, June 1, 2003; 144(6): 2368 - 2379.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. C. Borden, L. H. Baker, R. S. Bell, V. Bramwell, G. D. Demetri, B. L. Eisenberg, C. D. M. Fletcher, J. A. Fletcher, M. Ladanyi, P. Meltzer, et al.
Soft Tissue Sarcomas of Adults: State of the Translational Science
Clin. Cancer Res., June 1, 2003; 9(6): 1941 - 1956.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
I. Hedenfalk, M. Ringner, A. Ben-Dor, Z. Yakhini, Y. Chen, G. Chebil, R. Ach, N. Loman, H. Olsson, P. Meltzer, et al.
Molecular classification of familial non-BRCA1/BRCA2 breast cancer
PNAS, March 4, 2003; 100(5): 2532 - 2537.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
H. Sjogren, J. M. Meis-Kindblom, C. Orndal, P. Bergh, K. Ptaszynski, P. Aman, L.-G. Kindblom, and G. Stenman
Studies on the Molecular Pathogenesis of Extraskeletal Myxoid Chondrosarcoma--Cytogenetic, Molecular Genetic, and cDNA Microarray Analyses
Am. J. Pathol., March 1, 2003; 162(3): 781 - 792.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. Adeyinka, E. Emberley, Y. Niu, L. Snell, L. C. Murphy, H. Sowter, C. C. Wykoff, A. L. Harris, and P. H. Watson
Analysis of Gene Expression in Ductal Carcinoma in Situ of the Breast
Clin. Cancer Res., December 1, 2002; 8(12): 3788 - 3795.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. van de Rijn and B. P. Rubin
Gene Expression Studies on Soft Tissue Tumors
Am. J. Pathol., November 1, 2002; 161(5): 1531 - 1534.
[Full Text] [PDF]

Home page
 J. Virol.Home page
A. V. Moses, M. A. Jarvis, C. Raggo, Y. C. Bell, R. Ruhl, B. G. M. Luukkonen, D. J. Griffith, C. L. Wait, B. J. Druker, M. C. Heinrich, et al.
Kaposi's Sarcoma-Associated Herpesvirus-Induced Upregulation of the c-kit Proto-Oncogene, as Identified by Gene Expression Profiling, Is Essential for the Transformation of Endothelial Cells
J. Virol., July 17, 2002; 76(16): 8383 - 8399.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2001 by the American Association for Cancer Research.