Signaling by kinase domain mutants of KIT

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R-HSA-9669933
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Pathway
Species
Homo sapiens
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Signaling by kinase domain mutants of KIT
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Activating mutations in the kinase domain of KIT are found in a small number of cases of AML and melanoma, as well as in myeloproliferative syndromes, mastocytosis and germ cell tumors (Longley et al, 1996; 1999; Nagata et al, 1995; Beghini et al, 2000; Ning et al, 2001; Tian et al, 1999; Kemmer et al, 2004; reviewed in Roskoski, 2018; Meng and Carvajal, 2019). Mutations in the kinase domain and activation loop of KIT (encoded by exons 13, 14 and 17) also arise in gastrointestinal stromal tumors (GIST) as primary mutations (<1%) and as secondary resistance mutations in response to treatment with imatinib (Chen et al, 2004; Serrano et al, 2019; Gajiwala et al, 2008; McLean et al, 2008; reviewed in Antonescu, 2006; Roskoski, 2018; Wu et al, 2019; Corless et al, 2011). Activating kinase mutants of KIT are constitutively active in the absence of ligand and can be tyrosine phosphorylated in the absence of dimerization (Furitsu et al, 1993; Hirota et al, 1998; Tsujimura et al, 1994).

Literature References
PubMed ID Title Journal Year
16373716 Imatinib binding and cKIT inhibition is abrogated by the cKIT kinase domain I missense mutation Val654Ala

McLean, SR, Boshoff, C, Hartzoulakis, B, Gana-Weisz, M, Frow, R, Whelan, J, Selwood, D

Mol. Cancer Ther. 2005
22089421 Gastrointestinal stromal tumours: origin and molecular oncology

Barnett, CM, Corless, CL, Heinrich, MC

Nat. Rev. Cancer 2011
17193819 Gastrointestinal stromal tumor (GIST) pathogenesis, familial GIST, and animal models

Antonescu, CR

Semin Diagn Pathol 2006
29704617 The role of small molecule Kit protein-tyrosine kinase inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
7513208 Ligand-independent activation of c-kit receptor tyrosine kinase in a murine mastocytoma cell line P-815 generated by a point mutation

Kitamura, Y, Kanakura, Y, Matsuzawa, Y, Isozaki, K, Morimoto, M, Nomura, S, Furitsu, T, Tsujimura, T

Blood 1994
30707374 KIT as an Oncogenic Driver in Melanoma: An Update on Clinical Development

Carvajal, RD, Meng, D

Am J Clin Dermatol 2019
30792533 Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours

Heinrich, MC, Ketzer, J, Bauer, S, Zhu, M, Presnell, A, Raut, CP, George, S, Mannan, AM, Serrano, C, Yu, C, Sicinska, E, Tao, DL, Rubin, BP, Fletcher, JA, Mariño-Enríquez, A, Demetri, GD, Eilers, G, Czaplinski, JT, McKinley, A

Br. J. Cancer 2019
15342366 A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors

Raymond, AK, Choi, H, Frazier, ML, Wu, EF, Feig, BW, Hittelman, W, Ramdas, L, Velasco, MA, Patel, S, Oyedeji, CO, Pollock, RE, Prieto, VG, Benjamin, RS, Zhang, W, Burgess, MA, Hayes, KJ, Trent, JC, Chen, LL, Macapinlac, HA, Hunt, KK, Fuller, GN

Cancer Res. 2004
9438854 Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors

Kitamura, Y, Muhammad Tunio, G, Kanakura, Y, Matsuzawa, Y, Hanada, M, Moriyama, Y, Isozaki, K, Nishida, T, Hashimoto, K, Ishiguro, S, Kawano, K, Takeda, M, Kurata, A, Hirota, S, Shinomura, Y

Science 1998
7691885 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

Kitamura, Y, Kanakura, Y, Kanayama, Y, Matsuzawa, Y, Sugahara, H, Tono, T, Tsujimura, T, Butterfield, JH, Koshimizu, U, Ashman, LK, Kitayama, H, Furitsu, T, Ikeda, H

J. Clin. Invest. 1993
7479840 Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder

Nagata, H, Chowdhury, BA, Metcalfe, DD, Suzuki, Y, Worobec, AS, Tannenbaum, S, Oh, CK

Proc. Natl. Acad. Sci. U.S.A. 1995
16751810 Functional analyses and molecular modeling of two c-Kit mutations responsible for imatinib secondary resistance in GIST patients

Greco, A, Carbone, A, Ferrone, M, Pilotti, S, Casali, PG, Negri, T, Fermeglia, M, Lagonigro, MS, Gronchi, A, Pricl, S, Miselli, F, Tamborini, E, Pierotti, MA

Oncogene 2006
11378569 Activating mutations of c-kit at codon 816 confer drug resistance in human leukemia cells

Arceci, RJ, Ning, ZQ, Li, J

Leuk. Lymphoma 2001
10362788 Activating c-kit gene mutations in human germ cell tumors

Tian, Q, Krystal, GW, Moskaluk, CA, Frierson, HF

Am. J. Pathol. 1999
19164557 KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients

Quenzer, T, Emmett, MR, Deshmukh, GD, Lunney, EA, English, JM, Wu, JC, Christensen, J, Molina, D, He, YA, Zhang, Y, Greig, MJ, Demetri, GD, Yu, X, Diehl, W, McTigue, M, Gajiwala, KS, DiNitto, JP, Wells, PA, Jacques, SL, Zou, A, Zhang, HM, Marshall, AG

Proc. Natl. Acad. Sci. U.S.A. 2009
8589724 Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm

Lu, SZ, Jacobs, P, Modlin, I, Ding, TG, Ma, YS, Tang, LH, Longley, BJ, Duffy, T, Tyrrell, L, Langley, K

Nat. Genet. 1996
10660321 C-kit mutations in core binding factor leukemias

Beghini, A, Larizza, L, Peterlongo, P, Cairoli, R, Mecucci, C, Morra, E, Ripamonti, CB

Blood 2000
9990072 Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis

Ma, Y, Metcalfe, DD, Lu, SZ, Wang, X, Heitjan, D, Longley, BJ, Tyrrell, L, Tharp, M

Proc. Natl. Acad. Sci. U.S.A. 1999
30792534 Secondary KIT mutations: the GIST of drug resistance and sensitivity

Napolitano, A, Vincenzi, B

Br. J. Cancer 2019
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Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Rothfels, K  (2020-04-01)
Reviewed
Pilco-Janeta, D  (2020-03-13)
Serrano, C  (2020-03-13)
García-Valverde, A  (2020-03-13)
Created
Rothfels, K  (2019-12-03)
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