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Gene | KIT |
Variant | K642E |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | KIT K642E lies within the tyrosine kinase domain 1 (exon 13) of the Kit protein (PMID: 15990278). K642E results in constitutive phosphorylation of Kit and activation of downstream signaling (PMID: 15990278, PMID: 19802003), as well as transformation of cultured cells (PMID: 11073817). |
Associated Drug Resistance | |
Category Variants Paths |
KIT mutant KIT act mut KIT K642E KIT mutant KIT exon13 KIT K642E |
Transcript | NM_000222.3 |
gDNA | chr4:g.54728055A>G |
cDNA | c.1924A>G |
Protein | p.K642E |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_000222 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
NM_001385285.1 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
XM_017008178 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT K642E | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited proliferation of gastrointestinal stromal tumor cells harboring KIT K642E in culture (PMID: 21170960). | 21170960 |
KIT K642E | gastrointestinal stromal tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, a patient derived GIST cell line harboring KIT K642E demonstrated sensitivity to Iclusig (ponatinib) in culture (PMID: 25239608). | 25239608 |
KIT K642E | gastrointestinal stromal tumor | sensitive | Imatinib + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) and Gleevec (imatinib) combination treatment demonstrated enhanced antiproliferative activity in gastrointestinal stromal tumor cells harboring KIT K642E in culture (PMID: 25673643). | 25673643 |
KIT K642E | vulvar melanoma | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in partial response in a patient with recurrent vulval melanoma harboring KIT K642E, with reduction of tumor mass by 35% at 12 weeks (PMID: 20372153). | 20372153 |
KIT K642E | melanoma | predicted - sensitive | Nilotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT K642E demonstrating a partial response and a progression free survival of 5.8 months and overall survival of 18.6 months (PMID: 28327988). | 28327988 |
KIT K642E | gastrointestinal stromal tumor | sensitive | Axitinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited phosphorylation of KIT and downstream signaling, reduced proliferation, and induced cell-cycle arrest in a cultured gastrointestinal stromal tumor (GIST) cell line harboring KIT K642E, and inhibited proliferation of primary GIST cells harboring KIT K642E in culture (PMID: 31205508). | 31205508 |
KIT K642E | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of a gastrointestinal stromal tumor (GIST) cell line and primary GIST patient-derived cells harboring KIT K642E in culture (PMID: 31205508). | 31205508 |
KIT K642E | gastrointestinal stromal tumor | sensitive | Nintedanib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ofev (nintedanib) decreased Kit phosphorylation and downstream signaling, induced cell-cycle arrest and apoptosis, and inhibited proliferation of a gastrointestinal stromal tumor cell line and patient-derived cells harboring KIT K642E in culture, and suppressed tumor growth in cell line xenograft models (PMID: 35194937). | 35194937 |
KIT K642E | gastrointestinal stromal tumor | predicted - sensitive | IDRX-42 | Preclinical - Pdx | Actionable | In a preclinical study, IDRX-42 treatment inhibited mitosis and decreased tumor growth in a cell line xenograft model and a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT K642E (Cancer Res 2022;82(12_Suppl):Abstract nr 2666). | detail... |