Genomes and Genes
Gene Symbol: C-kit
Description: KIT proto-oncogene receptor tyrosine kinase
Alias: C-Kit, CD117, PBT, SCFR, mast/stem cell growth factor receptor Kit, c-Kit protooncogene, p145 c-kit, piebald trait protein, proto-oncogene c-Kit, proto-oncogene tyrosine-protein kinase Kit, soluble KIT variant 1, tyrosine-protein kinase Kit, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene-like protein
- Ríos Moreno M, Jaramillo S, Pereira Gallardo S, Vallejo A, Mora M, Garcia Escudero A, et al. Gastrointestinal stromal tumors (GISTs): CD117, DOG-1 and PKC? expression. Is there any advantage in using several markers?. Pathol Res Pract. 2012;208:74-81 pubmed publisher..Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Expression of CD117, DOG1 and PKC? was investigated immunohistochemically in a series of 99 paraffin-embedded GISTs in order to ..
- Andea A, Patel R, Ponnazhagan S, Kumar S, DeVilliers P, Jhala D, et al. Merkel cell carcinoma: correlation of KIT expression with survival and evaluation of KIT gene mutational status. Hum Pathol. 2010;41:1405-12 pubmed publisher..However, we did not identify KIT activating mutations in any of the tumors analyzed. ..
- Grabellus F, Worm K, Sheu S, Siffert W, Schmid K, Bachmann H. The prevalence of the c-kit exon 10 variant, M541L, in aggressive fibromatosis does not differ from the general population. J Clin Pathol. 2011;64:1021-4 pubmed publisher..The result classifies the M541L variant of c-kit exon 10 as a single nucleotide polymorphism. Because its prevalence does not differ between the AF and general populations, an association with AF tumourigenesis is unlikely. ..
- Zhang M, Ma Q, Hu H, Zhang D, Li J, Ma G, et al. Stem cell factor/c-kit signaling enhances invasion of pancreatic cancer cells via HIF-1? under normoxic condition. Cancer Lett. 2011;303:108-17 pubmed publisher..Therefore, our results suggest that the inhibition of both c-kit and HIF-1? may be an effective strategy for pancreatic cancer therapy. ..
- Zheng S, Huang K, Tao D, Pan Y. Gene mutations and prognostic factors analysis in extragastrointestinal stromal tumor of a Chinese three-center study. J Gastrointest Surg. 2011;15:675-81 pubmed publisher..Paraffin-embedded tissues from 25 cases of EGIST were analyzed for CD117, CD34, Ki-67, S-100, smooth muscle actin, and desmin expression by immunohistochemical method...
- Wilson T, Maric I, Simakova O, Bai Y, Chan E, Olivares N, et al. Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis. Haematologica. 2011;96:459-63 pubmed publisher..Unlike other mature lineages, mast cell survival is dependent on KIT and the presence of these two activating mutations may have a greater impact on the expansion of this cell compartment and in resultant disease severity. ..
- Ma D, Stence A, Bossler A, Hackman J, Bellizzi A. Identification of KIT activating mutations in paediatric solitary mastocytoma. Histopathology. 2014;64:218-25 pubmed publisher..Paediatric solitary mastocytoma is frequently associated with KIT activating mutations, in keeping with a clonal process. KIT mutational status appears insufficient to explain the divergent biology of childhood and adult-onset disease. ..
- Haller F, Cortis J, Helfrich J, Cameron S, Schüler P, Schwager S, et al. Epithelioid/mixed phenotype in gastrointestinal stromal tumors with KIT mutation from the stomach is associated with accelerated passage of late phases of the cell cycle and shorter disease-free survival. Mod Pathol. 2011;24:248-55 pubmed publisher
- El Serafi M, Bahnassy A, Ali N, Eid S, Kamel M, Abdel Hamid N, et al. The prognostic value of c-Kit, K-ras codon 12, and p53 codon 72 mutations in Egyptian patients with stage II colorectal cancer. Cancer. 2010;116:4954-64 pubmed publisher..The authors assessed the prognostic value of c-Kit (also called cluster of differentiation 117 [CD117] or KIT), cyclooxygenase-2 (COX-2), tumor protein 53 (p53), and Kirsten rat sarcoma viral oncogene homolog (K-ras) ..
- Kong Y, Si L, Zhu Y, Xu X, Corless C, Flaherty K, et al. Large-scale analysis of KIT aberrations in Chinese patients with melanoma. Clin Cancer Res. 2011;17:1684-91 pubmed publisher..The copy numbers of the KIT gene were analyzed by quantitative PCR, and protein expression levels of KIT (CD117) were determined by immunohistochemistry. The most common melanoma subtypes were acral (38.4%) and mucosal (33...
- Krasagakis K, Fragiadaki I, Metaxari M, Kruger Krasagakis S, Tzanakakis G, Stathopoulos E, et al. KIT receptor activation by autocrine and paracrine stem cell factor stimulates growth of merkel cell carcinoma in vitro. J Cell Physiol. 2011;226:1099-109 pubmed publisher..Blockade of KIT and the downstream signaling cascade at various levels results in inhibition of Merkel cell carcinoma growth in vitro, suggesting targets for therapy of this cancer. ..
- Cheng L, Roth L, Zhang S, Wang M, Morton M, Zheng W, et al. KIT gene mutation and amplification in dysgerminoma of the ovary. Cancer. 2011;117:2096-103 pubmed publisher..The purpose of this study was to analyze alterations of the KIT gene in a large series of dysgerminomas and correlate the findings with clinicopathological parameters...
- Regan J, Kendrick H, Magnay F, Vafaizadeh V, Groner B, Smalley M. c-Kit is required for growth and survival of the cells of origin of Brca1-mutation-associated breast cancer. Oncogene. 2012;31:869-83 pubmed publisher..The c-Kit signalling network has potential as a target for therapy and/or prevention in BRCA1-associated breast cancer. ..
- Luo L, Zeng J, Liang B, Zhao Z, Sun L, Cao D, et al. Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome. Exp Mol Pathol. 2011;91:596-602 pubmed publisher..We identified and isolated the tumorigenic cells as CD117(+)Lineage(-) from three different xenografts...
- Chau W, Ip C, Mak A, Lai H, Wong A. c-Kit mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/?-catenin-ATP-binding cassette G2 signaling. Oncogene. 2013;32:2767-81 pubmed publisher..The tumor-promoting microenvironment, such as hypoxia, could promote OTICs via upregulation of c-Kit expression. These results unravel an integral role for c-Kit in ovarian neoplastic processes and shed light on its mechanisms of action...
- Burford A, Little S, Jury A, Popov S, Laxton R, Doey L, et al. Distinct phenotypic differences associated with differential amplification of receptor tyrosine kinase genes at 4q12 in glioblastoma. PLoS ONE. 2013;8:e71777 pubmed publisher..Thus we have identified differential patterns of gene amplification and expression of RTKs at the 4q12 locus to be associated with specific phenotypes which may reflect their distinct underlying mechanisms. ..
- Chen P, Zong L, Zhao W, Shi L. Efficacy evaluation of imatinib treatment in patients with gastrointestinal stromal tumors: a meta-analysis. World J Gastroenterol. 2010;16:4227-32 pubmed..23 (95% CI: 0.73-2.10, P = 0.44, P(heterogeneity) = 0.42). Most patients with different genotypes of GIST and KIT exon 11-mutant will benefit from the individualized treatment of imatinib. ..
- Schoenewolf N, Bull C, Belloni B, Holzmann D, Tonolla S, Lang R, et al. Sinonasal, genital and acrolentiginous melanomas show distinct characteristics of KIT expression and mutations. Eur J Cancer. 2012;48:1842-52 pubmed publisher..P-ERK expression was preferentially found in metastases. KIT mutations predict treatment outcome with KIT inhibitors. Therefore, especially vulvar melanoma patients should be screened for activating KIT mutations. ..
- Gao J, Dang Y, Sun N, Li J, Shen L. C-KIT mutations were closely associated with the response to Imatinib in Chinese advanced gastrointestinal stromal tumor patients. Med Oncol. 2012;29:3039-45 pubmed publisher..C-KIT mutations were closely associated with Imatinib response and progression-free survival of Chinese advanced GIST patients. Other predictive markers for Imatinib would be further investigated. ..
- Soucie E, Hanssens K, Mercher T, Georgin Lavialle S, Damaj G, Livideanu C, et al. In aggressive forms of mastocytosis, TET2 loss cooperates with c-KITD816V to transform mast cells. Blood. 2012;120:4846-9 pubmed publisher..Taken together, these data demonstrate a oncogenic cooperation in mast cells and reveal TET2 mutation as a potential marker to diagnose and predict severe forms of mastocytosis. ..
- Novelli M, Rossi S, Rodriguez Justo M, Taniere P, Seddon B, Toffolatti L, et al. DOG1 and CD117 are the antibodies of choice in the diagnosis of gastrointestinal stromal tumours. Histopathology. 2010;57:259-70 pubmed publisher..Immunohistochemistry with a panel of antibodies [CD117, DOG1, protein kinase C (PKC)-theta, nestin, CD34, smooth muscle actin (SMA), desmin, S100 and CD171] was ..
- Pittoni P, Piconese S, Tripodo C, Colombo M. Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary off-target of tyrosine kinase inhibitors. Oncogene. 2011;30:757-69 pubmed publisher..Here, we summarize the tumor-intrinsic and -extrinsic roles of c-Kit in cancer and discuss TKIs with their on- and off-targets, with a special emphasis on MCs as paradigmatic c-Kit-dependent accomplices for tumor progression. ..
- Petrini I, Zucali P, Lee H, Pineda M, Meltzer P, Walter Rodriguez B, et al. Expression and mutational status of c-kit in thymic epithelial tumors. J Thorac Oncol. 2010;5:1447-53 pubmed publisher..No mutations were detected. c-kit expression is strongly but not exclusively related to thymic carcinoma histotype, and it is of prognostic value. Mutations are very rare. ..
- Ahmad F, D Souza W, Mandava S, Das B. Molecular analysis of WT1 and KIT mutations in patients from an Indian population with de novo acute myeloid leukemia: determination of incidence, distribution patterns, and report of a novel KIT mutation. Leuk Lymphoma. 2011;52:865-76 pubmed publisher..With respect to FLT3 and NPM1 mutations, WT1 was more predominant in FLT3 positive cases and less in NPM1 mutation cases, while no KIT mutation was found in FLT3/NPM1 positive cases. ..
- Wallander M, Willmore Payne C, Layfield L. C-KIT and PDGFRA zygosity in gastrointestinal stromal tumors: Correlation with tumor site, tumor size, exon, and CD117 immunohistochemistry. Appl Immunohistochem Mol Morphol. 2011;19:21-7 pubmed publisher..020). Zygosity of C-KIT or PDGFRA mutations did not correlate with most clinicopathologic features of GISTs including tumor size in our subset. However, homozygous mutant GISTs were associated with metastatic disease. ..
- Molderings G, Meis K, Kolck U, Homann J, Frieling T. Comparative analysis of mutation of tyrosine kinase kit in mast cells from patients with systemic mast cell activation syndrome and healthy subjects. Immunogenetics. 2010;62:721-7 pubmed publisher..The present findings support the idea that the systemic mast cell activation syndrome is a clonal disease most commonly associated with variable activating mutations in the tyrosine kinase kit. ..
- Gao X, Lin J, Li Y, Gao L, Wang X, Wang W, et al. MicroRNA-193a represses c-kit expression and functions as a methylation-silenced tumor suppressor in acute myeloid leukemia. Oncogene. 2011;30:3416-28 pubmed publisher..These data reveal a critical role for methylation-repressed miR-193a in myeloid leukemogenesis and the therapeutic promise of upregulating miR-193a expression for c-kit-positive AML. ..
- Wasag B, Niedoszytko M, Piskorz A, Lange M, Renke J, Jassem E, et al. Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis. Exp Hematol. 2011;39:859-65.e2 pubmed publisher..Finally, our findings support the hypothesis that not only KIT mutations but other additional genetic abnormalities are contributing to more advanced forms of the disease. ..
- Johansson I, Aaltonen K, Ebbesson A, Grabau D, Wigerup C, Hedenfalk I, et al. Increased gene copy number of KIT and VEGFR2 at 4q12 in primary breast cancer is related to an aggressive phenotype and impaired prognosis. Genes Chromosomes Cancer. 2012;51:375-83 pubmed publisher..Increased copy number of VEGFR2 and KIT thus has the potential of functioning as a novel predictive biomarker for selected targeted therapy particularly in the difficult-to-treat TNBC patient category. ..
- Hodi F, Corless C, Giobbie Hurder A, Fletcher J, Zhu M, Mariño Enríquez A, et al. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol. 2013;31:3182-90 pubmed publisher..Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities...
- Zong L, Chen P. Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumors: a meta-analysis. World J Surg Oncol. 2014;12:71 pubmed publisher..47 (95% CI, 0.25 to 0.90)). KIT mutations, compared with PDGFRA mutations and wild type, represent a poorer prognostic marker in high risk or malignant GISTs. ..
- Preto A, Moutinho C, Velho S, Oliveira C, Rebocho A, Figueiredo J, et al. A subset of colorectal carcinomas express c-KIT protein independently of BRAF and/or KRAS activation. Virchows Arch. 2007;450:619-26 pubmed..STI571/Gleevec increases apoptosis in CRC cell lines independently of its genetic profile, suggesting that STI571/Gleevec is likely to be an alternative drug for the clinical trials of CRC. ..
- Cho S, Kitadai Y, Yoshida S, Tanaka S, Yoshihara M, Yoshida K, et al. Deletion of the KIT gene is associated with liver metastasis and poor prognosis in patients with gastrointestinal stromal tumor in the stomach. Int J Oncol. 2006;28:1361-7 pubmed..Our data indicate that KIT mutations, especially deletions in exon 11, are markers of poor prognosis for gastric GISTs. ..
- Sandstedt J, Jonsson M, Lindahl A, Jeppsson A, Asp J. C-kit+ CD45- cells found in the adult human heart represent a population of endothelial progenitor cells. Basic Res Cardiol. 2010;105:545-56 pubmed publisher..The existence of an endothelial progenitor population within the heart might have future implications for developing methods of inducing neovascularization after myocardial infarction. ..
- Worobec A, Semere T, Nagata H, Metcalfe D. Clinical correlates of the presence of the Asp816Val c-kit mutation in the peripheral blood mononuclear cells of patients with mastocytosis. Cancer. 1998;83:2120-9 pubmed..Therefore, determination of the presence or absence of this mutation in PBMCs of mastocytosis patients offers a useful adjunct in determining the extent of workup and assigning prognosis in this complex and heterogeneous disease. ..
- Beadling C, Jacobson Dunlop E, Hodi F, Le C, Warrick A, Patterson J, et al. KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res. 2008;14:6821-8 pubmed publisher..A subset of cases was evaluated for BRAF and NRAS mutations. Immunohistochemistry was done to assess KIT (CD117) expression. KIT mutations were detected in 23% (3 of 13) of acral melanomas, 15...
- Wardelmann E, Losen I, Hans V, Neidt I, Speidel N, Bierhoff E, et al. Deletion of Trp-557 and Lys-558 in the juxtamembrane domain of the c-kit protooncogene is associated with metastatic behavior of gastrointestinal stromal tumors. Int J Cancer. 2003;106:887-95 pubmed
- Beghini A, Ripamonti C, Cairoli R, Cazzaniga G, Colapietro P, Elice F, et al. KIT activating mutations: incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication. Haematologica. 2004;89:920-5 pubmed..These results underline that the KIT gene is activated in AML characterized by distinct cytogenetic and molecular genetic patterns and represents the most frequently mutated target in adult CBFL. ..
- Bataille R, Pellat Deceunynck C, Robillard N, Avet Loiseau H, Harousseau J, Moreau P. CD117 (c-kit) is aberrantly expressed in a subset of MGUS and multiple myeloma with unexpectedly good prognosis. Leuk Res. 2008;32:379-82 pubmedb>CD117 (c-kit) was evaluated on normal plasma cells (PC) (n=10), PC of individuals with monoclonal gammopathy of undetermined significance (MGUS, n=12), malignant PC from patients with multiple myeloma (MM) either at diagnosis (n=83) or ..
- Tsuura Y, Hiraki H, Watanabe K, Igarashi S, Shimamura K, Fukuda T, et al. Preferential localization of c-kit product in tissue mast cells, basal cells of skin, epithelial cells of breast, small cell lung carcinoma and seminoma/dysgerminoma in human: immunohistochemical study on formalin-fixed, paraffin-embedded tissues. Virchows Arch. 1994;424:135-41 pubmed..The c-kit product may be a useful marker in diagnostic pathology of seminoma/dysgerminoma and SCLC among human solid tumours, and in distinction of SCLC from non-pulmonary small cell carcinoma...
- Dubreuil P, Letard S, Ciufolini M, Gros L, Humbert M, Casteran N, et al. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS ONE. 2009;4:e7258 pubmed publisher..Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicity. ..
- Sotlar K, Escribano L, Landt O, Möhrle S, Herrero S, Torrelo A, et al. One-step detection of c-kit point mutations using peptide nucleic acid-mediated polymerase chain reaction clamping and hybridization probes. Am J Pathol. 2003;162:737-46 pubmed
- Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell. 2007;130:323-34 pubmed
- Sihto H, Franssila K, Tanner M, Vasama Nolvi C, Sarlomo Rikala M, Nupponen N, et al. Platelet-derived growth factor receptor family mutations in gastrointestinal stromal tumours. Scand J Gastroenterol. 2006;41:805-11 pubmed..GISTs with PDGFRA mutations often have reduced expression of the KIT protein in immunohistochemistry, suggesting that immunohistochemistry may be potentially useful in identification of such GISTs. ..
- Sihto H, Tynninen O, Halonen M, Puputti M, Karjalainen Lindsberg M, Kukko H, et al. Tumour microvessel endothelial cell KIT and stem cell factor expression in human solid tumours. Histopathology. 2009;55:544-53 pubmed publisher..034). Intratumoral microvessels of several types of human malignant tumours express KIT. Tumour cell SCF expression and absence of marked endothelial cell KIT expression are novel adverse prognostic features in glioblastoma. ..
- Larizza L, Magnani I, Beghini A. The Kasumi-1 cell line: a t(8;21)-kit mutant model for acute myeloid leukemia. Leuk Lymphoma. 2005;46:247-55 pubmed..Independent findings on the same model system provide complementary insights into designing strategies for treatment of CBF leukemia associated with mutations in the KIT catalytic domain. ..
- Fuster O, Barragan E, Bolufer P, Cervera J, Larráyoz M, Jimenez Velasco A, et al. Rapid detection of KIT mutations in core-binding factor acute myeloid leukemia using high-resolution melting analysis. J Mol Diagn. 2009;11:458-63 pubmed publisher..These findings verify that HRM is a reliable, rapid, and sensitive method for KIT mutation screening. Furthermore, our study corroborates the unfavorable prognosis associated with exon 17 KIT mutations. ..
- Liu X, Bai C, Xie Q, Feng F, Xu Z, Ma D. Prognostic value of KIT mutation in gastrointestinal stromal tumors. World J Gastroenterol. 2005;11:3948-52 pubmed..C-kit mutation is a undoubtedly pivotal event in GIST and may be associated with poor prognosis. Evaluation of C-kit gene mutation may have both prognosis and therapeutic significances. ..
- Holtkamp N, Okuducu A, Mucha J, Afanasieva A, Hartmann C, Atallah I, et al. Mutation and expression of PDGFRA and KIT in malignant peripheral nerve sheath tumors, and its implications for imatinib sensitivity. Carcinogenesis. 2006;27:664-71 pubmed..In summary, PDGFRA, PDGF and KIT dysregulation as well as growth inhibition of cell culture S462 by imatinib may suggest that MPNST patients benefit from treatment with imatinib. ..
- Furitsu T, Tsujimura T, Tono T, Ikeda H, Kitayama H, Koshimizu U, et al. 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. J Clin Invest. 1993;92:1736-44 pubmed..These results suggest that conversion of Asp-816 to Val in human c-kitR may be an activating mutation and responsible for the constitutive activation of c-kitR in HMC-1 cells...
- Kitamura Y, Hirotab S. Kit as a human oncogenic tyrosine kinase. Cell Mol Life Sci. 2004;61:2924-31 pubmed..The interrelationship between the type of Kit gain-of-function mutations and the therapeutic effect of imatinib mesylate has been well characterized in GISTs. Kit is interesting from both a biological and clinical view-point...
- Kikuchi H, Yamamoto M, Hiramatsu Y, Baba M, Ohta M, Kamiya K, et al. Effect of loss of heterozygosity of the c-kit gene on prognosis after hepatectomy for metastatic liver gastrointestinal stromal tumors. Cancer Sci. 2007;98:1734-9 pubmed..LOH of the c-kit gene in metastatic liver seems to be a common event, and LOH of the c-kit gene in resected liver GIST may be a helpful factor in the prediction of the post-recurrent prognosis of patients with liver metastasis. ..
- Smalley K, Contractor R, Nguyen T, Xiao M, Edwards R, Muthusamy V, et al. Identification of a novel subgroup of melanomas with KIT/cyclin-dependent kinase-4 overexpression. Cancer Res. 2008;68:5743-52 pubmed publisher..This group of melanomas may be a subpopulation for which imatinib or other KIT inhibitors may constitute optimal therapy. ..
- Yamazaki K, Sakamoto M, Ohta T, Kanai Y, Ohki M, Hirohashi S. Overexpression of KIT in chromophobe renal cell carcinoma. Oncogene. 2003;22:847-52 pubmed..As overexpression of KIT might be involved in tumor growth, KIT could be a new therapeutic target in this special type of RCC. ..
- Beghini A, Magnani I, Ripamonti C, Larizza L. Amplification of a novel c-Kit activating mutation Asn(822)-Lys in the Kasumi-1 cell line: a t(8;21)-Kit mutant model for acute myeloid leukemia. Hematol J. 2002;3:157-63 pubmed
- Aichberger K, Gleixner K, Mirkina I, Cerny Reiterer S, Peter B, Ferenc V, et al. Identification of proapoptotic Bim as a tumor suppressor in neoplastic mast cells: role of KIT D816V and effects of various targeted drugs. Blood. 2009;114:5342-51 pubmed publisher..Targeting of Bcl-2 family members by drugs promoting Bim (re)-expression, or by BH3-mimetics such as obatoclax, may be an attractive therapy concept in SM. ..
- Blume Jensen P, Siegbahn A, Stabel S, Heldin C, Ronnstrand L. Increased Kit/SCF receptor induced mitogenicity but abolished cell motility after inhibition of protein kinase C. EMBO J. 1993;12:4199-209 pubmed..Our data suggest that PKC is involved in a negative feedback loop which regulates the Kit/SCF-R and that the activity of PKC determines whether the effect of SCF will be preferentially mitogenic or motogenic. ..
- Weiler S, Mou S, DeBerry C, Keller J, Ruscetti F, Ferris D, et al. JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor. Blood. 1996;87:3688-93 pubmed..These data demonstrate that SCF induces tyrosine phosphorylation of JAK2 and suggest that JAK2 is a component of the SCF signal transduction pathway. ..
- Yavuz A, Lipsky P, Yavuz S, Metcalfe D, Akin C. Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene. Blood. 2002;100:661-5 pubmed
- Heinrich M, Corless C, Duensing A, McGreevey L, Chen C, Joseph N, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708-10 pubmed..Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs. ..
- Sommer G, Agosti V, Ehlers I, Rossi F, Corbacioglu S, Farkas J, et al. Gastrointestinal stromal tumors in a mouse model by targeted mutation of the Kit receptor tyrosine kinase. Proc Natl Acad Sci U S A. 2003;100:6706-11 pubmed..Importantly, these results demonstrate that constitutive Kit signaling is critical and sufficient for induction of GIST and hyperplasia of interstitial cells of Cajal. ..
- Kemmer K, Corless C, Fletcher J, McGreevey L, Haley A, Griffith D, et al. KIT mutations are common in testicular seminomas. Am J Pathol. 2004;164:305-13 pubmed..These findings suggest that activating KIT mutations may contribute to tumorigenesis in a subset of seminomas, but are not involved in NSGCT...
- Raspollini M, Amunni G, Villanucci A, Baroni G, Taddei A, Taddei G. c-KIT expression and correlation with chemotherapy resistance in ovarian carcinoma: an immunocytochemical study. Ann Oncol. 2004;15:594-7 pubmed
- Subramanian S, West R, Corless C, Ou W, Rubin B, Chu K, et al. Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles. Oncogene. 2004;23:7780-90 pubmed..These gene products could serve as highly selective therapeutic targets in GISTs containing the KIT or PDGFRA mutational types with which they are associated. ..
- Kohl T, Schnittger S, Ellwart J, Hiddemann W, Spiekermann K. KIT exon 8 mutations associated with core-binding factor (CBF)-acute myeloid leukemia (AML) cause hyperactivation of the receptor in response to stem cell factor. Blood. 2005;105:3319-21 pubmed..Our data show that KIT exon 8 mutations represent gain-of-function mutations and might represent a new molecular target for treatment of CBF leukemias. ..
- Masson K, Heiss E, Band H, Ronnstrand L. Direct binding of Cbl to Tyr568 and Tyr936 of the stem cell factor receptor/c-Kit is required for ligand-induced ubiquitination, internalization and degradation. Biochem J. 2006;399:59-67 pubmed..Taken together, our findings reveal novel insights into the mechanisms by which Cbl negatively regulates c-Kit-mediated signalling. ..