c-Kit is an Oncogene first found in a Feline Retrovirus Besmer, P., J. E. Murphy, P. C. George, F. Qui, P. J. Bergold, L. Lederman, H. W. Snyder Jr., D. Brodeur, E. E. Zukerman, and W. D. Hardy A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. Nature (Lond.). 320:

c-Kit is a Receptor Tyrosine Kinase that is Activated in Human Cancers Yarden, Y. et al. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. The EMBO Journal :

c-Kit Activates Many Signaling Pathways Corless, C.L., Heinrich, M.C. Molecular Pathobiology of Gastrointestinal Stromal Sarcomas. Annu. Rev. Pathol. Mech. Dis :

c-Kit is Essential for Proper Hematopoiesis and Intestinal Function Kimura Y, Ding B, Imai N, Nolan DJ, Butler JM, et al. (2011) c-Kit- Mediated Functional Positioning of Stem Cells to Their Niches Is Essential for Maintenance and Regeneration of Adult Hematopoiesis. PLoS ONE 6(10): e Maeda, H. et al. Requirement of c-kit for development of intestinal pacemaker system. Development 116, (1992)

GIST is a Mesenchymal Tumor that Arises in the Smooth Muscle Wall of GI Tract Corless, C.L., Heinrich, M.C. Molecular Pathobiology of Gastrointestinal Stromal Sarcomas. Annu. Rev. Pathol. Mech. Dis :

c-Kit Mutations in GIST Result in Constitutive Activation Seiichi Hirota et al. Gain-of-Function Mutations of c-kit in Human Gastrointestinal Stromal Tumors. Science, New Series, Vol. 279, No (Jan. 23, 1998), pp

Mutations Activating c-Kit Result in Cell Proliferation and Tumor Growth Seiichi Hirota et al. Gain-of-Function Mutations of c-kit in Human Gastrointestinal Stromal Tumors. Science, New Series, Vol. 279, No (Jan. 23, 1998), pp

c-Kit Mutations Are Found in 80% of GISTs, With the Majority of Mutations Occurring in the Juxtamembrane Domain Corless, C.L., Heinrich, M.C. Molecular Pathobiology of Gastrointestinal Stromal Sarcomas. Annu. Rev. Pathol. Mech. Dis :

GISTs Are Treatable by the Kinase Inhibitor Imatinib/Gleevec Corless, C.L., Heinrich, M.C. Molecular Pathobiology of Gastrointestinal Stromal Sarcomas. Annu. Rev. Pathol. Mech. Dis :

Imatinib Resistance Leads to Use of Secondary Therapies/Cocktail Therapy

References Besmer, P., J. E. Murphy, P. C. George, F. Qui, P. J. Bergold, L. Lederman, H. W. Snyder Jr., D. Brodeur, E. E. Zukerman, and W. D. Hardy A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. Nature (Lond.). 320: Yarden, Y. et al. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. The EMBO Journal : Corless, C.L., Heinrich, M.C. Molecular Pathobiology of Gastrointestinal Stromal Sarcomas. Annu. Rev. Pathol. Mech. Dis : Kimura Y, Ding B, Imai N, Nolan DJ, Butler JM, et al. (2011) c-Kit-Mediated Functional Positioning of Stem Cells to Their Niches Is Essential for Maintenance and Regeneration of Adult Hematopoiesis. PLoS ONE 6(10): e Maeda, H. et al. Requirement of c-kit for development of intestinal pacemaker system. Development 116, (1992) Hirota, S. et al. Gain-of-Function Mutations of c-kit in Human Gastrointestinal Stromal Tumors. Science, New Series, Vol. 279, No (Jan. 23, 1998), pp Taniguchi, M. et al. Effect of c-kit mutations on prognosis of gastrointestinal stromal tumors. Cancer Res 1999;59: Furitsu T, Tsujimura T, Tono T, et al. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J Clin Invest 1993;92Primary structure of c-kit: relationship with the CSF-1/PDGF receptor tyrosine kinase family- oncogenic activation of v-kit involves deletion of extracellular domain and C terminus. EMBO Journal :