| Target General Information |
| Target ID |
T57700
|
| Target Name |
Mast/stem cell growth factor receptor Kit (KIT) |
| Gene Name |
KIT |
| Species |
Homo sapiens |
| UniProt ID |
KIT_HUMAN |
| Sequence |
MRGARGAWDFLCVLLLLLRVQTGSSQPSVSPGEPSPPSIHPGKSDLIVRVGDEIRLLCTD
PGFVKWTFEILDETNENKQNEWITEKAEATNTGKYTCTNKHGLSNSIYVFVRDPAKLFLV
DRSLYGKEDNDTLVRCPLTDPEVTNYSLKGCQGKPLPKDLRFIPDPKAGIMIKSVKRAYH
RLCLHCSVDQEGKSVLSEKFILKVRPAFKAVPVVSVSKASYLLREGEEFTVTCTIKDVSS
SVYSTWKRENSQTKLQEKYNSWHHGDFNYERQATLTISSARVNDSGVFMCYANNTFGSAN
VTTTLEVVDKGFINIFPMINTTVFVNDGENVDLIVEYEAFPKPEHQQWIYMNRTFTDKWE
DYPKSENESNIRYVSELHLTRLKGTEGGTYTFLVSNSDVNAAIAFNVYVNTKPEILTYDR
LVNGMLQCVAAGFPEPTIDWYFCPGTEQRCSASVLPVDVQTLNSSGPPFGKLVVQSSIDS
SAFKHNGTVECKAYNDVGKTSAYFNFAFKGNNKEQIHPHTLFTPLLIGFVIVAGMMCIIV
MILTYKYLQKPMYEVQWKVVEEINGNNYVYIDPTQLPYDHKWEFPRNRLSFGKTLGAGAF
GKVVEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIVNLLGAC
TIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAALYKNLLHSKESSCSDSTNE
YMDMKPGVSYVVPTKADKRRSVRIGSYIERDVTPAIMEDDELALDLEDLLSFSYQVAKGM
AFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWMAPES
IFNCVYTFESDVWSYGIFLWELFSLGSSPYPGMPVDSKFYKMIKEGFRMLSPEHAPAEMY
DIMKTCWDADPLKRPTFKQIVQLIEKQISESTNHIYSNLANCSPNRQKPVVDHSVRINSV
GSTASSSQPLLVHDDV [Homo sapiens]
|
| Drug and Corresponding Resistance Mutations |
| Mutation Info |
Missense: A829P |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[7] |
| Mutation Prevalence |
2 out of 78 patients |
|
| Mutation Info |
Missense: C809G |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[6] |
| Mutation Prevalence |
8 out of 10 patients in all KIT mutations |
|
| Mutation Info |
Missense: D579 |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[4] |
| Mutation Prevalence |
1 out of 33 patients |
|
| Mutation Info |
Missense: D716N |
| Drugs |
|
| Mutation Info |
Missense: D816A |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[7] |
| Mutation Prevalence |
1 out of 78 patients |
|
| Mutation Info |
Missense: D816E |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[13], [14] |
| Mutation Prevalence |
14 out of 32 patients in all KIT mutations |
|
| Mutation Info |
Missense: D816G |
| Drugs |
| Drug Name |
Crizotinib |
Drug Info
|
[1] |
| Targeted Disease |
Lung Cancer |
|
|
|
| Mutation Info |
Missense: D816H |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[6] |
| Mutation Prevalence |
8 out of 10 patients in all KIT mutations |
|
| Mutation Info |
Missense: D820A |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[8], [7] |
| Mutation Prevalence |
21 out of 33 patients in all KIT mutations |
|
| Mutation Info |
Missense: D820E |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[4] |
| Mutation Prevalence |
3 out of 33 patients |
|
| Mutation Info |
Missense: D820G |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[8] |
| Mutation Prevalence |
21 out of 33 patients in all KIT mutations |
|
| Mutation Info |
Missense: D820Y |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[4] |
| Mutation Prevalence |
3 out of 33 patients |
|
| Mutation Info |
Missense: H697Y |
| Drugs |
|
| Mutation Info |
Missense: K642E |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[5], [4] |
| Mutation Prevalence |
1 out of 33 patients |
|
| Mutation Info |
Missense: N680K |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[4] |
| Mutation Prevalence |
1 out of 33 patients |
|
| Mutation Info |
Missense: N822K |
| Drugs |
| Drug Name |
Sunitinib |
Drug Info
|
[3] |
| Targeted Disease |
Acute Myeloid Leukaemia; Gastrointestinal Stromal Tumor |
|
| Drug Name |
Imatinib |
Drug Info
|
[6] |
| Mutation Prevalence |
8 out of 10 patients in all KIT mutations |
|
| Mutation Info |
Missense: N822Y |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[4], [8], [12] |
| Mutation Prevalence |
3 out of 33 patients |
|
| Mutation Info |
Missense: S709F |
| Drugs |
|
| Mutation Info |
Missense: S821F |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[16] |
| Mutation Prevalence |
1 out of 3 patients |
|
| Mutation Info |
Missense: T670E |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[13], [4] |
| Mutation Prevalence |
14 out of 32 patients in all KIT mutations |
|
| Mutation Info |
Missense: T670I |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[7] |
| Mutation Prevalence |
3 out of 78 patients |
|
| Mutation Info |
Missense: V559I |
| Drugs |
|
| Mutation Info |
Missense: V654A |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[4] |
| Mutation Prevalence |
9 out of 33 patients |
|
| Mutation Info |
Missense: Y578C |
| Drugs |
| Drug Name |
Imatinib |
Drug Info
|
[4] |
| Mutation Prevalence |
2 out of 33 patients |
|
| Mutation Info |
Missense: Y823D |
| Drugs |
| Drug Name |
Sunitinib |
Drug Info
|
[2] |
| Targeted Disease |
Acute Myeloid Leukaemia; Gastrointestinal Stromal Tumor |
|
| Drug Name |
Imatinib |
Drug Info
|
[5] |
| Mutation Prevalence |
9 out of 32 patients |
|
| References |
| REF 1 |
An Activating KIT Mutation Induces Crizotinib Resistance in ROS1-Positive Lung Cancer. J Thorac Oncol. 2016 Aug;11(8):1273-81.
|
| REF 2 |
Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25.
|
| REF 3 |
Surgical intervention for imatinib and sunitinib-resistant gastrointestinal stromal tumors. Int J Clin Oncol. 2011 Dec;16(6):741-5.
|
| REF 4 |
Massively parallel sequencing fails to detect minor resistant subclones in tissue samples prior to tyrosine kinase inhibitor therapy. BMC Cancer. 2015 Apr 15;15:291.
|
| REF 5 |
Molecular mechanisms of secondary imatinib resistance in patients with gastrointestinal stromal tumors. J Cancer Res Clin Oncol. 2010 Jul;136(7):1065-71.
|
| REF 6 |
Clonal evolution of resistance to imatinib in patients with metastatic gastrointestinal stromal tumors. Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5398-405.
|
| REF 7 |
Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol. 2008 Nov 20;26(33):5352-9.
|
| REF 8 |
Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol. 2006 Oct 10;24(29):4764-74.
|
| REF 9 |
Juxtamembrane-type c-kit gene mutation found in aggressive systemic mastocytosis induces imatinib-resistant constitutive KIT activation. Lab Invest. 2007 Apr;87(4):365-71.
|
| REF 10 |
Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis. Exp Hematol. 2011 Aug;39(8):859-65.e2.
|
| REF 11 |
Secondary c-Kit mutations confer acquired resistance to RTK inhibitors in c-Kit mutant melanoma cells. Pigment Cell Melanoma Res. 2013 Jul;26(4):518-26.
|
| REF 12 |
Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol. 2008 Sep;216(1):64-74.
|
| REF 13 |
Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res. 2006 Mar 15;12(6):1743-9.
|
| REF 14 |
Surgical intervention following imatinib treatment in patients with advanced gastrointestinal stromal tumors (GISTs). J Surg Oncol. 2008 Jul 1;98(1):27-33.
|
| REF 15 |
Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology. 2005 Feb;128(2):270-9.
|
| REF 16 |
Detection of KIT and PDGFRA mutations in the plasma of patients with gastrointestinal stromal tumor. Target Oncol. 2015 Dec;10(4):597-601.
|
