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Profile Name | KIT V654A |
Gene Variant Detail | |
Relevant Treatment Approaches |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT W557_K558del KIT V654A | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and decreased tumor volume (PMID: 25239608). | 25239608 |
KIT W557_K558del KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in reduced cell viability, decreased tumor volume, and tumor regression (PMID: 25239608). | 25239608 |
KIT W557_K558del KIT V654A | Advanced Solid Tumor | no benefit | Imatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated no response to treatment with Gleevec (imatinib) in both culture and xenograft models (PMID: 25239608). | 25239608 |
KIT W557_K558del KIT V654A | Advanced Solid Tumor | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated resistance to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). | 25239608 |
KIT V560_L576del KIT V654A | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_L576del and KIT V654A demonstrated sensitivity to treatment with Sutent (sunitinib) (PMID: 25239608). | 25239608 |
KIT exon11 KIT V654A | gastrointestinal stromal tumor | sensitive | Imatinib + MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a Gleevec (imatinib)-resistant gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion mutation and KIT V654A in culture (PMID: 27370604). | 27370604 |
KIT V560D KIT V654A | Advanced Solid Tumor | sensitive | Motesanib Diphosphate | Preclinical - Cell culture | Actionable | In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing a KIT V560D/V654A double mutation in culture (PMID: 20633291). | 20633291 |
KIT V560del KIT V654A | Advanced Solid Tumor | sensitive | Nilotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Tasigna (nilotinib) inhibited proliferation of transformed cells expressing a KIT V560del/V654A double mutation in culture (PMID: 17699867). | 17699867 |
KIT W557_K558del KIT V654A | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Pdx | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and resulted in tumor regression in patient-derived xenograft models of Gleevec (imatinib)-resistant gastrointestinal stromal tumor harboring KIT W557_K558del and V654A (PMID: 29093181). | 29093181 |
KIT V559D KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT V559D and KIT V654A were sensitive to treatment with Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 |
KIT V560D KIT V654A | Advanced Solid Tumor | resistant | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT V560D and KIT V654A were resistant to Flumatinib in culture (PMID: 24205792). | 24205792 |
KIT K558_V560del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT V654A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT K558_V560del mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). | 18488160 |
KIT V569_L576del KIT V654A KIT N822K | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT V654A and KIT N822K were identified as secondary mutations in a patient with gastrointestinal stromal tumor harboring a primary KIT V569_L576del mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). | 18488160 |
KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD3229 suppressed Kit signaling and cell growth in culture, and inhibited tumor growth in a cell line xenograft model of gastrointestinal stromal tumor harboring KIT V560_Y578del and KIT V654A (PMID: 32350132). | 32350132 |
KIT W557_K558del KIT V654A | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Pdx | Actionable | In a preclinical study, AZD3229 inhibited Kit signaling and tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT V654A, which was established from a patient who did not respond to Gleevec (imatinib) treatment (PMID: 32350132). | 32350132 |
KIT V559D KIT V654A | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V654A and KIT V559D in culture (PMID: 31205508). | 31205508 |
KIT V559D KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V654A and KIT V559D in culture (PMID: 31205508). | 31205508 |
KIT V654A KIT D816V | Advanced Solid Tumor | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT V654A demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078). | 31270078 |
KIT V654A KIT D816V | Advanced Solid Tumor | predicted - sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT V654A demonstrated some sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078). | 31270078 |
KIT V560D KIT V654A | Advanced Solid Tumor | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT V560D and KIT V654A demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT V560D alone in culture (PMID: 31270078). | 31270078 |
KIT V559_G565del KIT V654A KIT A829P | gastrointestinal stromal tumor | predicted - sensitive | Ripretinib | Case Reports/Case Series | Actionable | In a Phase I trial, treatment with Qinlock (ripretinib) decreased circulating tumor DNA, resulted in stable disease lasting over 26 months in a patient with gastrointestinal stromal tumor harboring a primary KIT V559_G565del mutation and two acquired resistance mutations, KIT V654A and KIT A829P (PMID: 31085175; NCT02571036). | 31085175 |
KIT V560_L576del KIT V654A | gastrointestinal stromal tumor | sensitive | HQP1351 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, HQP1351 treatment inhibited Kit downstream signalling, resulted in cell cycle arrest and apoptosis in a Gleevec (imatinib)-resistant gastrointestinal stromal tumor (GIST) cell line harboring KIT V560_L576del and V654A in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 31673329). | 31673329 |
KIT W557_K558del KIT V654A | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT V654A, which was established from a patient who did not respond to Gleevec (imatinib) treatment (PMID: 32350132). | 32350132 |
KIT W557_K558del KIT V654A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with AZD3229 in both culture and cell line xenograft models, resulting in reduced cell viability, decreased KIT signaling, and tumor regression (PMID: 32350132). | 32350132 |
KIT W557_K558del KIT V654A | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ayvakit (avapritinib) failed to inhibit cell growth or KIT signaling in culture and did not suppress tumor growth in cell line xenograft models of transformed cells expressing KIT W557_K558del and KIT V654A (PMID: 32350132). | 32350132 |
KIT W557_K558del KIT V654A | Advanced Solid Tumor | resistant | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) failed to reduce cell viability and inhibit KIT signaling in transformed cells expressing KIT W557_K558del and KIT V654A in culture (PMID: 32350132). | 32350132 |
KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Sutent (sunitinib) inhibited growth of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and inhibited tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 |
KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Ripretinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Qinlock (ripretinib) resulted in slight decreases in cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, but failed to suppress tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 |
KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | resistant | Avapritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ayvakit (avapritinib) failed to decrease cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and did suppress tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 |
KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Gleevec (imatinib) failed to decrease cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and did suppress tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 |
KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 |
KIT V560D KIT V654A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
KIT V560D KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated sensitivity to Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
KIT V560D KIT V654A | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
KIT V560D KIT V654A | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated resistance to treatment with Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 |
KIT V560D KIT V654A | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT V560D alone in culture (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated sensitivity to Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Ayvakit (avapritinib) in culture (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT A502_Y503dup alone in culture (PMID: 32350132). | 32350132 |
KIT exon11 KIT V654A | gastrointestinal stromal tumor | sensitive | Copanlisib | Preclinical - Cell culture | Actionable | In a preclinical study, Aliqopa (copanlisib) inhibited cell growth and PI3K signaling in a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT V654A in culture (PMID: 32371592). | 32371592 |
KIT exon11 KIT V654A | gastrointestinal stromal tumor | predicted - sensitive | Copanlisib + Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Aliqopa (copanlisib) and Gleevec (imatinib) demonstrated enhanced cell growth inhibition but did not result in increased apoptosis of gastrointestinal stromal tumor cells harboring a KIT exon 11 deletion and KIT V654A compared to either agent alone in culture (PMID: 32371592). | 32371592 |
KIT V560_L576del KIT V654A | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT V560_L576del and V654A with overexpression of GPR20 (IHC score 3+) (PMID: 33579785). | 33579785 |
KIT V560_L576del KIT V654A | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT V560_L576del and V654A with overexpression of GPR20 (IHC score 3+) (PMID: 33579785). | 33579785 |
KIT V560_L576del KIT V654A | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT V560_L576del and V654A with overexpression of GPR20 (IHC score 3+) demonstrated resistance to treatment with Gleevec (imatinib) (PMID: 33579785). | 33579785 |
KIT exon 11 del KIT V654A | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT V654A in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... |
KIT exon 9 ins KIT V654A | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 9 insertion and KIT V654A in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... |
KIT Q556_I571del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, KIT V654A was identified as a secondary mutation in a patient with a gastrointestinal stromal tumor harboring a primary KIT Q556_I571del mutation who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) (PMID: 35041493; NCT01991379). | 35041493 |
KIT Q556_V559delinsHT KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, KIT V654A was identified as a secondary resistance mutation in a patient with a gastrointestinal stromal tumor harboring a primary KIT Q556_V559delinsHT mutation who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) (PMID: 35041493; NCT01991379). | 35041493 |
KIT E554_K558del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, KIT V654A was identified as a secondary resistance mutation in a patient with a gastrointestinal stromal tumor harboring a primary KIT E554_K558del mutation who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) treatment (PMID: 35041493; NCT01991379). | 35041493 |
KIT V559D KIT V654A | Advanced Solid Tumor | predicted - sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D and V654A demonstrated decreased proliferation in response to Ofev (nintedanib) in culture, but were less sensitive to treatment compared to cells expressing either KIT V559D or KIT V654A alone (PMID: 35194937). | 35194937 |
KIT V559D KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V559D and V654A in culture (PMID: 35194937). | 35194937 |
KIT V559D KIT V654A | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D and V654A were resistant to Ayvakit (avapritinib) treatment in culture (PMID: 35194937). | 35194937 |
KIT V559D KIT V654A | Advanced Solid Tumor | resistant | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D and V654A were resistant to Qinlock (ripretinib) treatment in culture (PMID: 35194937). | 35194937 |
KIT E554_Y570del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with gastrointestinal stromal tumor harboring KIT E554_Y570del progressed following an initial response to Gleevec (imatinib), and was found to have acquired the secondary resistance mutation KIT V654A (PMID: 18294292). | 18294292 |
KIT W557_K558del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, three patients with gastrointestinal stromal tumors harboring KIT W557_K558del progressed following an initial response to Gleevec (imatinib), and were found to have acquired the secondary resistance mutation KIT V654A (PMID: 18294292). | 18294292 |
KIT W557_E561del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, two patients with gastrointestinal stromal tumors harboring KIT W557_E561del progressed following an initial response to Gleevec (imatinib), and were found to have acquired the secondary resistance mutation KIT V654A (PMID: 18294292). | 18294292 |
KIT M552_D572del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, two patients with gastrointestinal stromal tumors harboring KIT M552_D572del progressed following an initial response to Gleevec (imatinib), and were found to have acquired the secondary resistance mutation KIT V654A (PMID: 18294292). | 18294292 |
KIT V559_T574del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with gastrointestinal stromal tumor harboring KIT V559_T574del progressed following an initial response to Gleevec (imatinib), and was found to have acquired the secondary resistance mutation KIT V654A in one lesion (PMID: 18294292). | 18294292 |
KIT Q556_W557del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with gastrointestinal stromal tumor harboring KIT Q556_W557del progressed following an initial response to Gleevec (imatinib), and was found to have acquired the secondary resistance mutation KIT V654A (PMID: 18294292). | 18294292 |