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Gastrointestinal stromal tumors in a mouse model by targeted mutation of the Kit receptor tyrosine kinase
Open accessAbstract
Oncogenic Kit mutations are found in somatic gastrointestinal (GI) stromal tumors (GISTs) and mastocytosis. A mouse model for the study of constitutive activation of Kit in oncogenesis has been produced by a knock-in strategy introducing a Kit exon 11-activating mutation into the mouse genome based on a mutation found in a case of human familial GIST syndrome. Heterozygous mutant Kit V558 Δ /+ mice develop symptoms of disease and eventually die from pathology in the GI tract. Patchy hyperplasia of Kit-positive cells is evident within the myenteric plexus of the entire GI tract. Neoplastic lesions indistinguishable from human GISTs were observed in the cecum of the mutant mice with high penetrance. In addition, mast cell numbers in the dorsal skin were increased. Therefore Kit V558 Δ /+ mice reproduce human familial GISTs, and they may be used as a model for the study of the role and mechanisms of Kit in neoplasia. Importantly, these results demonstrate that constitutive Kit signaling is critical and sufficient for induction of GIST and hyperplasia of interstitial cells of Cajal.
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Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors
Demetri, G. D., von Mehren, M., Blanke, C. D., Van den Abbeele, A. D., Eisenberg, B., Roberts, P. J., Heinrich, M. C., Tuveson, D. A., Singer, S., Janicek, M., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020461 · Cited by 4,389
Efficient in vivo manipulation of mouse genomic sequences at the zygote stage.
Lakso, M., Pichel, J. G., Gorman, J. R., Sauer, B., Okamoto, Y., Lee, E., Alt, F. W., & Westphal, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.5860 · Cited by 1,125
Cited by
Gastrointestinal stromal tumours: origin and molecular oncology
Corless, C. L., Barnett, C. M., & Heinrich, M. C. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3143 · Cited by 891
Antonescu, C. R., Besmer, P., Guo, T., Arkun, K., Hom, G., Koryotowski, B., Leversha, M. A., Jeffrey, P. D., Desantis, D., Singer, S., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-2245 · Cited by 836
Self-citationBalachandran, V. P., Cavnar, M. J., Zeng, S., Bamboat, Z. M., Ocuin, L. M., Obaid, H., Sorenson, E. C., Popow, R., Ariyan, C., Rossi, F., et al. (2011) · Nature Medicine · doi:10.1038/nm.2438 · Cited by 521
Self-citationDeMatteo, R. P., Gold, J. S., Saran, L., Gönen, M., Liau, K. H., Maki, R. G., Singer, S., Besmer, P., Brennan, M. F., & Antonescu, C. R. (2008) · Cancer · doi:10.1002/cncr.23199 · Cited by 503
Self-citationChen, L. L., Trent, J. C., Wu, E. F., Fuller, G. N., Ramdas, L., Zhang, W., Raymond, A. K., Prieto, V. G., Oyedeji, C. O., Hunt, K. K., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0085 · Cited by 339
Metadata
- Authors
- Sommer, G., Agosti, V., Ehlers, I., Rossi, F., Corbacioglu, S., Farkas, J., Moore, M., Manova, K., Antonescu, C. R., & Besmer, P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2003-05-16
- Volume
- 100
- Issue
- 11
- Pages
- 6706-6711
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2123571541
- Cited by
- 244
- References
- 2
- FWCI
- 16.50
- Type
- journal article
- Language
- en
- Open access
- green
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- Sommer, G., Agosti, V., Ehlers, I., Rossi, F., Corbacioglu, S., Farkas, J., Moore, M., Manova, K., Antonescu, C. R., & Besmer, P. (2003). Gastrointestinal stromal tumors in a mouse model by targeted mutation of the Kit receptor tyrosine kinase. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1037763100
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