KIT(cKIT) mutations are present in approximately 8-25% of cases of acute myeloid leukemia and have a higher prevalence in the favorable cytogenetic risk group including core binding factor (CBF) AMLs (ie, (t(8;21)(q22;q22)(RUNX1-RUNX1T1), inv(16)(p13q22)(CBFB-MYH11)) or normal karyotype AML. Mutations of KIT in AML are most common in KIT exon 17 (within the activation loop of the tyrosine kinase domain) but may also occur in KIT exons 8 (extracellular portion of the receptor implicated in dimerization), 9-11 (juxtamembrane/transmembrane domains). The presence of KIT mutations has been reported to be associated with a poorer survival and/or higher risk of relapse than expected for patients with the t(8;21)(q22;q22)(RUNX1-RUNX1T1), and to a lesser extent, in inv(16) AML. KIT mutations are also important in systemic mastocytosis and various mast cell disorders; over 90% of cases of systemic mastocytosis carry mutations in exon 17 of KIT (most commonly D816V or rarely D816H, D816Y or other variants). In patients with mastocytosis, the KIT mutations may be detectable in non-mast cell hematopoietic cells. The KIT D816V mutation has been shown to be resistant to imatinib; other KIT mutations may show variable responses to imatinib. The KIT D816V mutant has been reported to be sensitive to other tyrosine kinase inhibitors. In the context of core binding factor AMLs, the KIT mutation status can help direct therapeutic management.

The M541L mutation has been implicated in hematological malignancies. It may help to identify a subgroup of cases who may benefit from low dose imatinib therapy. KIT mutations are also associated with Gastro Intestinal Stromal Tumors. The KIT variant M541L was originally thought to be associated with increased risk of certain tumors such as aggressive fibromatosis (AF; Dufresne et al., 2010). However, larger scale studies have shown that the prevalence of this mutation within AF does not differ from that of the general population and this variant was not found to be tumor-specific, classifying it as a single nucleotide polymorphism and non-pathogenic (Grabellus et al., 2011).

Approximately 50-60% of the oncogenic mutations in Gastrointestinal stromal tumors (GIST) are present in Exon 11 of the KIT gene. The E554K variant is present in Exon 11 of the KIT gene. Identification of GIST genotype is important given the availability of targeted therapy with KIT/PDGFRA tyrosine kinase inhibitors (eg, imatinib, sunitinib, etc).

KIT mutations occur in approximately 80% of patients with gastrointestinal stromal tumors. The major region of KIT mutation in GIST is within exon 11, occurring in about 65% of patients. KIT exon 11 mutations are activating mutations and are typically sensitive to treatment with Imatinib.

KIT mutations occur in approximately 15-20% of patients with mucosal melanomas. The majority ofKIT mutations occur within exon 11 and they are less frequent in other exons. The N822K mutation in exon 17 occurs within the kinase domain of KIT. Mutant KIT proteins have increased kinase activity and transforming activity in vitro. Although KIT activating mutations in exons 11 and 13 are typically sensitive to treatment with Imatinib, there was no response to treatment noted in patients harboring mutations in exon 17 (Ref. 4).

c-kit (CD117) is a growth factor receptor of the tyrosine kinase subclass III family, normally expressed in a variety of human tissues. Gain-of-function mutations of the c-kit gene have been identified that produce ligand-independent activation of c-kit and cell proliferation. Some of these mutations appear causative in the pathogenesis of adult mastocytosis and most gastrointestinal stromal tumors (GISTs). c-kit receptor and its ligand have been demonstrated in human colon cancer cell lines. Some studies have shown high frequency of c-Kit overexpression in stage II colon cancer patients (59.3%) with significant correlation between c-Kit overexpression and reduced disease free survival. However, other studies failed to demonstrate c-kit expression in a significant number of colorectal cancers suggesting that c-kit kinase activation is not a prominent pathogenetic feature of colorectal cancers. Role of c-Kit continues to be studied in colon cancers.

KIT mutations occur in approximately 85% of patients with gastrointestinal stromal tumors (GIST), while Exon 9 is mutated in approximately 10 ~ 15% of all KIT-mutated GIST. Compared to patients with KIT exon 11 mutations, patients with exon 9 mutations tumors show intermediate sensitivity to imatinib. Median duration of benefit from imatinib is approximately 7~12 months compared to 23 months for patients with exon 11 mutations. Patients with exon 9 mutations are more likely to respond to second line sunitinib than patients with other KIT/PDGFRA mutations.

KIT mutations are seen in up to 17% of cutaneous melanomas. The V559A mutation in exon 11 occurs within the juxtamembrane domain. In vitro studies have shown that mutant KIT proteins have increased kinase activity. KIT activating mutations in exons 11 and 13 are typically sensitive to treatment with Imatinib. There are multiple clinical trials available for patients with melanomas harboring KIT alterations.

KIT is a growth factor receptor of the tyrosine kinase subclass III family, normally expressed in a variety of human tissues. Somatic mutations of KIT are only identified in ~ 4% of thymic carcinoma, but KIT protein overexpression has been observed in up to 88% of cases. Valine at amino acid position 560 (V560) is located in exon 11 within the juxtamembrane domain of KIT, and an in-frame deletion of V560 results in an activating mutation. A case report has described a patient with thymic carcinoma harboring KIT V560del who had a partial response to imatinib. In another case, patient who has kit mutation in his thymic carcinoma achieved 27 moths of disease control with imatinib followed by sunitinib. Results should be interpreted in conjunction with other laboratory and clinical findings.

In AML, presence of exon 17 mutations in KIT may confer an adverse prognosis or increased relapse rate. However, its significance in brain tumors is yet to be determined.

In AML, presence of exon 17 mutations in KIT may confer an adverse prognosis or increased relapse rate. However, its significance in renal cancer is yet to be determined.

KIT, also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117, is a growth factor receptor of the tyrosine kinase subclass III family, normally expressed in a variety of tissue types. Signaling through CD117 plays a role in cell survival, proliferation, and differentiation. Altered forms of this receptor may be associated with some types of cancers. Somatic mutations of KIT in lung adenocarcinoma are relatively rare, reported up to 3.3% of the cases. The predictive and prognostic significance of KIT mutations in lung adenocarcinomas needs further elucidation. Results should be interpreted in conjunction with other laboratory and clinical findings.

KIT, also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117, is a growth factor receptor of the tyrosine kinase subclass III family, normally expressed in a variety of tissue types. Signaling through CD117 plays a role in cell survival, proliferation, and differentiation. Altered forms of this receptor may be associated with some types of cancers. Somatic mutations of KIT in esophageal cancers are relatively rare, observed in up to 3.3% of the cases. The predictive and prognostic significance of KIT mutations in esophageal cancers needs further elucidation. Results should be interpreted in conjunction with other laboratory and clinical findings.

The V654A c-KIT kinase domain mutation has been associated with imatinib-resistant GIST relapse, representing about 47% of all GIST secondary mutations. GIST harboring KIT V654A is still sensitive to Sunitinib and Sorafenib. drug: Nilotinib, Sunitinib

This gene is a known cancer gene.

This gene is a known cancer gene.

Nilotinib Dasatinib Sorafenib Imatinib

Imatinib

Sorafenib

Dasatinib Nilotinib

Imatinib

Imatinib

Imatinib

Sunitinib

Regorafenib Sunitinib Imatinib

Regorafenib Sunitinib Imatinib

Imatinib

Imatinib

Dasatinib

Imatinib

Sunitinib

Nilotinib Sorafenib Imatinib

Imatinib

Nilotinib Dasatinib Sunitinib Imatinib

Sorafenib

Sunitinib

Imatinib

Imatinib

Imatinib

Imatinib

Imatinib

Regorafenib

Imatinib

Imatinib

Sunitinib

Sunitinib Imatinib Nilotinib

Imatinib

Imatinib

Imatinib

Imatinib

Sorafenib

Sorafenib

Imatinib

Sunitinib

Sunitinib Imatinib

Nilotinib Dasatinib Sorafenib Regorafenib Sunitinib

Sunitinib

Regorafenib Sunitinib Imatinib

Imatinib Nilotinib Dasatinib Sorafenib

Imatinib

Imatinib

Imatinib

Imatinib

Sorafenib

Sunitinib

Imatinib

Imatinib Dasatinib

Imatinib

Imatinib

Sorafenib

Imatinib Nilotinib

Imatinib

Sunitinib Imatinib

Sunitinib

Imatinib

KIT, also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117, is a growth factor receptor of the tyrosine kinase subclass III family, normally expressed in a variety of tissue types. Signaling through CD117 plays a role in cell survival, proliferation, and differentiation. KIT is found in approximately 1% of glioblastomas. The KIT D45N variant is in the extracellular domain, however, its effect on protein function is unknown. The clinical significance of KIT in glioblastoma and the clinicopathologic effect of this variant remains to be further elucidated.

KIT (CD117) is a growth factor receptor of the tyrosine kinase subclass III family, normally expressed in a variety of human tissues. Gain-of-function mutations of the KIT gene have been identified that produce ligand-independent activation of KIT and cell proliferation. KIT receptor and its ligand have been demonstrated in human colon cancer cell lines. Some studies have shown high frequency of KIT overexpression in stage II colon cancer patients (59.3%) with significant correlation between KIT overexpression and reduced disease free survival. However, other studies failed to demonstrate KIT expression in a significant number of colorectal cancers suggesting that KIT kinase activation is not a prominent pathogenetic feature of colorectal cancers. Role of KIT continues to be studied in colon cancers. KIT K807N missense mutation is known to be oncogenic. Several tyrosine kinase inhibitors against KIT are available, mainly for gastrointestinal stromal tumors and melanoma. The role of these targeted therapies in colorectal carcinomas need to be further elucidated.

The proto-oncogene KIT encodes a type 3 transmembrane receptor tyrosine kinase. c-kit (CD117) is a growth factor receptor of the tyrosine kinase subclass III family, normally expressed in a variety of human tissues. Gain-of-function mutations of the c-kit gene have been identified that produce ligand-independent activation of c-kit and cell proliferation. Some of these mutations appear causative in the pathogenesis of adult mastocytosis and most gastrointestinal stromal tumors (GISTs). Activating KIT mutations occur in 80 - 90% of GISTs and several small molecule tyrosine kinase inhibitors (TKIs) targeting KIT that have been approved by the US Food and Drug Administration with the efficacy of each TKI strongly depending on the location of the activating KIT mutation. c-kit receptor and its ligand have been demonstrated in human colon cancer cell lines. Some studies have shown high frequency of c-Kit overexpression in stage II colon cancer patients (59.3%) with significant correlation between c-Kit overexpression and reduced disease free survival. However, other studies failed to demonstrate c-kit expression in a significant number of colorectal cancers suggesting that c-kit kinase activation is not a prominent pathogenetic feature of colorectal cancers. The role of c-Kit continues to be studied in colon cancers. The KIT D52N mutation likely represent an oncogenic gain of function mutation.

KIT, also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117, is a growth factor receptor of the tyrosine kinase subclass III family, normally expressed in a variety of tissue types. Signaling through CD117 plays a role in cell survival, proliferation, and differentiation. Altered forms of this receptor may be associated with many types of cancers including hematopoietic malignancies, gastrointestinal stromal tumors, and various carcinomas and sarcomas. KIT G565V lies within the cytoplasmic domain of the Kit protein; this variant has been documented in the scientific literature (in melanoma). While its effect on Kit protein function is unknown, it is reported in ClinVar as likely benign germline variant (https://preview.ncbi.nlm.nih.gov/clinvar/variation/41600/).

KIT, also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117, is a growth factor receptor of the tyrosine kinase subclass III family, normally expressed in a variety of tissue types. Signaling through CD117 plays a role in cell survival, proliferation, and differentiation. Altered forms of this receptor may be associated with some types of cancers. Somatic mutations of KIT in lung adenocarcinoma are relatively rare, reported up to 3.3% of the cases. The predictive and prognostic significance of KIT mutations in lung adenocarcinomas needs further elucidation. According to ClinVar, the clinical significance of this particular variant C844Y is unknown (https://preview.ncbi.nlm.nih.gov/clinvar/variation/409781/). Results should be interpreted in conjunction with other laboratory and clinical findings.