KIT
Primary Author(s)*
Brian Davis PhD
Synonyms
"KIT Proto-Oncogene Receptor Tyrosine Kinase"; "V-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog"; PBT; "Stem Cell Factor Receptor"; SCFR; "Cellular KIT"; C-Kit; CD117; MASTC
Genomic Location
Cytoband: 4q12
Genomic Coordinates:
chr4:55,524,085-55,606,881(GRCh37/hg19)
chr4:55,524,085-55,606,881(GRCh37/hg19)
Cancer Category/Type
KIT mutations are prevalent in many cancers, including gastrointestinal stromal tumors (GIST, a soft tissue sarcoma) (90%)[3], genetical tract cancers (22%), hematopoietic and lymphoid cancers (13.8%), and Melanomas (7%) (see COSMIC).
Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms
- RUNX1-RUNX1T1 Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1
- CBFB-MYH11 Acute Myeloid Leukemia (AML) with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
Mutations that cause constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity and point mutations in the kinase domain that result in a constitutively activated kinase.
Mutations of KIT have been shown to have prognostic significance among AML with t(8;21)(q22;q22) (RUNX1-RUNXT1) and inv(16)(p13.1q22)/ t(16;16)(p13.1;q22) (CBFB-MYH11), in which they are associated with a poor prognosis. These KIT mutations most commonly occur within exon 8 and 17. [1]. KIT mutations occurs primarily in a subset of leukemias containing inv(16) or t(8;21), so-called core factor binding AML. Apart from exon 17 mutations, also internal tandem duplications in exon 11 have been described. Prognosis. Presence of D816V mutation in KIT is a poor prognostic factor [see Atlas of Genetics and Cytogenetics in Oncology and Haematology].
GIST (gastrointestinal stromal tumors)
Mast cell disease
Melanoma
Gene Overview
The KIT gene encodes tyrosine kinase protein receptor and is the human homolog of the proto-oncogene first described in the feline sarcoma virus, v-KIT. Stem Cell Factor protein (SCF) is the ligand which binds to Kit protein, causing dimerization and activation of signaling cascades which are involved in a wide variety of cellular roles including: regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myeloid leukemia, and other diseases The Kit protein . (adapted from UniProt Description).
Common Alteration Types
Mutations in KIT are found clustered in the C-terminal tyrosine kinase domain, the majority occurring at position D816 (see COSMIC). . The presence of the KIT D816V mutation in malignaicies confers Imatinib resistance [4]. In AML, the most common KIT mutations are in-frame, internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity.
| Copy Number Loss | Copy Number Gain | LOH | Loss-of-Function Mutation | Gain-of-Function Mutation | Translocation/Fusion |
|---|---|---|---|---|---|
| X |
Internal Pages
External Links
KIT by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information
KIT by COSMIC - sequence information, expression, catalogue of mutations
KIT by CIViC - general knowledge and evidence-based variant specific information
KIT by St. Jude ProteinPaint mutational landscape and matched expression data.
KIT by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs
KIT by Cancer Index - gene, pathway, publication information matched to cancer type
KIT by OncoKB - mutational landscape, mutation effect, variant classification
KIT by My Cancer Genome - brief gene overview
KIT by UniProt - protein and molecular structure and function
KIT by Pfam - gene and protein structure and function information
KIT by GeneCards - general gene information and summaries
KIT by NCBI Gene - general gene information and summaries
KIT by OMIM - compendium of human genes and genetic phenotypes
KIT by LOVD(3) - Leiden Open Variation Database
KIT by TICdb - database of Translocation breakpoints In Cancer
References
1. Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.
2. Schafer, E.S. . et al. (2015). Molecular Genetics of Acute Lymphoblastic Leukemia in The Molecular Basis of Cancer, 4th edition. Mendelsohn, J, Howley, PM, Israel, MA, Gray, JW, Thompson, CB. Editors. Elsevier Press: Philadelphia, USA, p395-406.
3. Rubin B.P et al. (2001). KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res. 61: 8118-21. PMID: 11719439
4. Da Silva Figueiredo Celestino Gomes, P. et al., (2016). PLoS One 11:e0160165. PMID 27467080 doi: 10.1371/journal.pone.0160165.
Notes
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