c-Kit is an Oncogene first found in a Feline Retrovirus

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. 1986. A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. Nature (Lond.). 320:415-421.

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. 1987. 6: 3341-3351.

c-Kit Activates Many Signaling Pathways

Corless, C.L., Heinrich, M.C. Molecular Pathobiology of Gastrointestinal Stromal Sarcomas. Annu. Rev. Pathol. Mech. Dis. 2008.3:557-586.

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): e26918.

Maeda, H. et al. Requirement of c-kit for development of intestinal pacemaker system. Development 116, 369-375 (1992)

GIST is a Mesenchymal Tumor that Arises in the Smooth Muscle Wall of GI Tract


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. 5350 (Jan. 23, 1998), pp. 577-580

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. 5350 (Jan. 23, 1998), pp. 577-580

c-Kit Mutations Are Found in 80% of GISTs, With the Majority of Mutations Occurring in

the Juxtamembrane Domain


GISTs Are Treatable by the Kinase Inhibitor Imatinib/Gleevec


Imatinib Resistance Leads to Use of Secondary Therapies/Cocktail Therapy

http://en.wikipedia.org/wiki/File:Sunitinib.svg

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. 1986. A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. Nature (Lond.). 320:415-421.

• Yarden, Y. et al. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. The EMBO Journal. 1987. 6: 3341-3351.

• Corless, C.L., Heinrich, M.C. Molecular Pathobiology of Gastrointestinal Stromal Sarcomas. Annu. Rev. Pathol. Mech. Dis. 2008.3:557-586.

• 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): e26918.

• Maeda, H. et al. Requirement of c-kit for development of intestinal pacemaker system. Development 116, 369-375 (1992)• Hirota, S. et al. Gain-of-Function Mutations of c-kit in Human Gastrointestinal Stromal Tumors. Science, New Series, Vol. 279,

No. 5350 (Jan. 23, 1998), pp. 577-580 • Taniguchi, M. et al. Effect of c-kit mutations on prognosis of gastrointestinal stromal tumors. Cancer Res 1999;59:4297-4300• 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. 1988. 7: 1003-1011.

c-Kit is an Oncogene first found in a Feline Retrovirus

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