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Biology of Gastrointestinal Stromal Tumors

From the Oregon Health & Science University Cancer Institute, Department of Pathology, and Division of Hematology and Oncology, Oregon Health & Science University and Veterans Affairs Medical Center, Portland, OR; and Department of Pathology, Brigham & Women's Hospital, Boston, MA

Address reprint requests to Michael Heinrich, MD, R&D-19 3710 SW US Veterans Hospital Rd, Portland, OR 97201; e-mail: heinrich{at}ohsu.edu

Once a poorly defined pathologic oddity, in recent years, gastrointestinal stromal tumor (GIST) has emerged as a distinct oncogenetic entity that is now center stage in clinical trials of kinase-targeted therapies. This review charts the rapid progress that has established GIST as a model for understanding the role of oncogenic kinase mutations in human tumorigenesis. Approximately 80% to 85% of GISTs harbor activating mutations of the KIT tyrosine kinase. In a series of 322 GISTs (including 140 previously published cases) studied by the authors in detail, mutations in the KIT gene occurred with decreasing frequency in exons 11 (66.1%), 9 (13%), 13 (1.2%), and 17 (0.6%). In the same series, a subset of tumors had mutations in the KIT-related kinase gene PDGF receptor alpha (PDGFRA), which occurred in either exon 18 (5.6%) or 12 (1.5%). The remainder of GISTs (12%) were wild type for both KIT and PDGFRA. Comparative studies of KIT-mutant, PDGFRA-mutant, and wild-type GISTs indicate that there are many similarities between these groups of tumors but also important differences. In particular, the responsiveness of GISTs to treatment with the kinase inhibitor imatinib varies substantially depending on the exonic location of the KIT or PDGFRA mutation. Given these differences, which have implications both for the diagnosis and treatment of GISTs, we propose a molecular-based classification of GIST. Recent studies of familial GIST, pediatric GIST, and variant forms of GIST related to Carney's triad and neurofibromatosis type 1 are discussed in relationship to this molecular classification. In addition, the role of mutation screening in KIT and PDGFRA as a diagnostic and prognostic aid is emphasized in this review.

The authors regret that, because of space constraints, it was not possible to include all pertinent references in this review.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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				S. R. McLean, M. Gana-Weisz, B. Hartzoulakis, R. Frow, J. Whelan, D. Selwood, and C. Boshoff Imatinib binding and cKIT inhibition is abrogated by the cKIT kinase domain I missense mutation Val654Ala Mol. Cancer Ther., December 1, 2005; 4(12): 2008 - 2015. [Abstract] [Full Text] [PDF]

				C. Cutcliffe, D. Kersey, C.-C. Huang, Y. Zeng, D. Walterhouse, E. J. Perlman, and for the Renal Tumor Committee of the Children's On Clear Cell Sarcoma of the Kidney: Up-regulation of Neural Markers with Activation of the Sonic Hedgehog and Akt Pathways Clin. Cancer Res., November 15, 2005; 11(22): 7986 - 7994. [Abstract] [Full Text] [PDF]

				C. Cullinane, D. S. Dorow, M. Kansara, N. Conus, D. Binns, R. J. Hicks, L. K. Ashman, G. A. McArthur, and D. M. Thomas An In vivo Tumor Model Exploiting Metabolic Response as a Biomarker for Targeted Drug Development Cancer Res., November 1, 2005; 65(21): 9633 - 9636. [Abstract] [Full Text] [PDF]

				G Rossi, G Sartori, R Valli, F Bertolini, N Bigiani, L Schirosi, A Cavazza, and G Luppi The value of c-kit mutational analysis in a cytokeratin positive gastrointestinal stromal tumour J. Clin. Pathol., September 1, 2005; 58(9): 991 - 993. [Abstract] [Full Text] [PDF]

				M. Van Glabbeke, J. Verweij, P. G. Casali, A. Le Cesne, P. Hohenberger, I. Ray-Coquard, M. Schlemmer, A. T. van Oosterom, D. Goldstein, R. Sciot, et al. Initial and Late Resistance to Imatinib in Advanced Gastrointestinal Stromal Tumors Are Predicted by Different Prognostic Factors: A European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group Study J. Clin. Oncol., August 20, 2005; 23(24): 5795 - 5804. [Abstract] [Full Text] [PDF]

				C. L. Corless, A. Schroeder, D. Griffith, A. Town, L. McGreevey, P. Harrell, S. Shiraga, T. Bainbridge, J. Morich, and M. C. Heinrich PDGFRA Mutations in Gastrointestinal Stromal Tumors: Frequency, Spectrum and In Vitro Sensitivity to Imatinib J. Clin. Oncol., August 10, 2005; 23(23): 5357 - 5364. [Abstract] [Full Text] [PDF]

				C. Tarn, E. Merkel, A. A. Canutescu, W. Shen, Y. Skorobogatko, M. J. Heslin, B. Eisenberg, R. Birbe, A. Patchefsky, R. Dunbrack, et al. Analysis of KIT Mutations in Sporadic and Familial Gastrointestinal Stromal Tumors: Therapeutic Implications through Protein Modeling Clin. Cancer Res., May 15, 2005; 11(10): 3668 - 3677. [Abstract] [Full Text] [PDF]

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