• What is KIT?
  • KIT in GIST
  • KIT Exon 13 Mutation
  • Clinical Trials


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.

Related Pathways

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 https://www.padiracinnovation.org/content/disease/gist/kit/?tab=0 (Updated December 7).

Last Updated: December 7, 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 https://www.padiracinnovation.org/content/disease/gist/kit/ (Updated September 29).

Last Updated: September 29, 2014

KIT Exon 13 Mutation in GIST

Location of mutation Tyrosine kinase 1 (TK1) domain/ATP binding pocket
Frequency of KIT mutations in GIST ~85% (Heinrich et al. 2003)
Frequency of KIT exon 13 mutations in KIT-mutated GIST 1–3% (Heinrich et al. 2003)
Implications for Targeted Therapeutics
Response to imatinib Confers sensitivity as a primary mutation;
Confers resistance as a secondary mutation
Response to sunitinib Sensitive in in vitro studies;
Too few patients in imatinib naïve or second-line settings to determine
Response to sorafenib Unknown at this time
Response to nilotinib Unknown at this time
Response to dasatinib Unknown at this time

Although only a limited number of patients with primary KIT exon 13 mutations have been included in clinical trials with imatinib, clinical benefit appears to be similar to that of patients with exon 11 mutations (Heinrich et al. 2008).

In vitro studies suggest that sunitinib inhibits KIT double mutants harboring exon 13 mutations while imatinib does not. Too few patients have been included in clinical trials to have an accurate understanding of their response to treatment; however, small series suggest sunitinib may provide some benefit over imatinib in this setting (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. 2014. KIT Exon 13 Mutation in GIST. My Cancer Genome https://www.padiracinnovation.org/content/disease/gist/kit/49/ (Updated August 8).

Last Updated: August 8, 2014

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