• What is KIT?
  • KIT in GIST
  • KIT Exon 17 Mutation


KIT (also called CD117) is a receptor tyrosine kinase (RTK) expressed on a wide variety of cell types. The ligand for KIT is stem cell factor (SCF). The binding of SCF to the extracellular domain of KIT induces receptor dimerization and activation of downstream signaling pathways, including the PI3K-AKT-mTOR pathway, the RAS-RAF-MEK-ERK pathway, and the signal transducer and activator of transcription 3 (acute-phase response factor), or STAT3, pathway, all of which are involved in mediating pro-growth and pro-survival signals within the cell (Figure 1).

Mutant KIT has been implicated in the pathogenesis of several cancers including melanoma, acute leukemia, and gastrointestinal stromal tumor (GIST; Heinrich et al. 2003; Hirota et al. 1998).

The discovery of KIT mutations revolutionized the treatment of GISTs. The use of imatinib mesylate (Gleevec), an oral KIT inhibitor leads to rapid, substantial, and durable tumor responses (Demetri et al. 2002). Not all KIT mutations are associated with equal sensitivity to imatinib (Heinrich et al. 2008); some are more sensitive to second-generation KIT inhibitors.


Figure 1.
Schematic of KIT signaling pathways. The binding of SCF, to the KIT receptor tyrosine kinase results in activation of the MAPK signaling pathway (RAS-RAF-MEK-ERK), the PI3K pathway (PI3K-AKT-mTOR), and the STAT3 pathway. The letter "K" within the schema denotes the tyrosine kinase domain. ​

Contributors: Christine M. Lovly, M.D., Ph.D., Jeff Sosman, M.D., William Pao, M.D., Ph.D. (through April 2014)

Suggested Citation: Lovly, C., J. Sosman, W. Pao. 2015. KIT. My Cancer Genome http://www.mycancergenome.org/content/disease/gist/kit/?tab=0 (Updated June 16).

Last Updated: June 16, 2015


KIT is mutated in ~85% of GIST (Heinrich et al. 2003). The vast majority of KIT mutations are found in exon 11 (juxtamembrane domain; ~70%), exon 9 (extracellular dimerization motif; 10–15%), exon 13 (tyrosine kinase 1 (TK1) domain; 1–3%), and exon 17 (tyrosine kinase 2 (TK2) domain and activation loop; 1–3%; Heinrich et al. 2003). Secondary KIT mutations in exons 13, 14, 17, and 18 are commonly identified in post-imatinib biopsy specimens, after patients have developed acquired resistance. ​

Contributors: Robert G. Maki, M.D., Ph.D., FACP, Vicki Keedy, M.D., M.S.C.I.

Suggested Citation: Maki, R., V. Keedy. 2014. KIT in GIST. My Cancer Genome http://www.mycancergenome.org/content/disease/gist/kit/ (Updated September 29).

Last Updated: September 29, 2014

KIT Exon 17 Mutation in GIST

Location of mutation Tyrosine kinase 2 (TK2) domain and activation loop
Frequency of KIT mutations in GIST ~85% (Heinrich et al. 2003)
Frequency of KIT exon 17 mutations in KIT-mutated GIST 0.0% (Minárik et al. 2012)
Implications for Targeted Therapeutics
Response to imatinib Primary mutation sensitive in vitro;
Confers resistance as a secondary mutation
Response to sunitinib Confers resistance as secondary mutation;
Too few people treated in imatinib-naïve setting to determine activity
Response to sorafenib Unknown at this time
Response to nilotinib Unknown at this time
Response to dasatinib Unknown at this time

KIT exon 17 mutations have been identified as primary mutations in a small percentage of patients with some responses seen. In vitro studies suggest that KIT double mutants harboring exon 17 mutations are resistant to both imatinib and sunitinib. Too few patients have been included in clinical trials to have an accurate understanding of their response to treatment; however, sunitinib appears to provide little benefit (Heinrich et al. 2008).


Figure 1.
Schematic of KIT. Domains encoded by various exons are shown.

Contributors: Robert G. Maki, M.D., Ph.D., FACP, Vicki Keedy, M.D., M.S.C.I.

Suggested Citation: Maki, R., V. Keedy. 2012. KIT Exon 17 Mutation in GIST. My Cancer Genome http://www.mycancergenome.org/content/disease/gist/kit/52/ (Updated November 30).

Last Updated: November 30, 2012

KIT-Associated Gastrointestinal Stromal Tumor Clinical Trials

Great effort was made to include all clinical trials relevant for this mutation. However, the completeness of this information cannot be guaranteed.

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