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==Primary Author(s)*==
==Primary Author(s)*==
Brian Davis PhD
__TOC__
__TOC__
==Synonyms==
==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==
==Genomic Location==
'''Cytoband:''' Put your text here. EXAMPLE: 17p13.1
'''Cytoband:''' 4q12
'''Genomic Coordinates:'''
'''Genomic Coordinates:'''
chr4:55,524,085-55,606,881(GRCh37/hg19)
chr4:55,524,085-55,606,881(GRCh37/hg19)
==Cancer Category/Type==
==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%) ([https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=kit see COSMIC]).
[http://www.ccga.io/index.php/HAEM4:Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]
- [http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_with_t(8;21)(q22;q22.1) RUNX1-RUNX1T1 Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1]
- [http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_with_inv(16)(p13.1q22)_or_t(16;16)(p13.1;q22) 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 [[http://atlasgeneticsoncology.org/Genes/KITID127.html see Atlas of Genetics and Cytogenetics in Oncology and Haematology]].
GIST (gastrointestinal stromal tumors)
Mast cell disease
Melanoma
[http://www.ccga.io/index.php/Melanoma_skin_Cancer Melanoma Skin Cancer]
==Gene Overview==
==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 . ([https://www.uniprot.org/uniprot/P10721 adapted from UniProt Description]).
==Common Alteration Types==
==Common Alteration Types==
Mutations in KIT are found clustered in the C-terminal tyrosine kinase domain, the majority occurring at position D816 ([https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=kit 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.
{| class="wikitable sortable"
{| class="wikitable sortable"
! Copy Number Loss !! Copy Number Gain !! LOH !! Loss-of-Function Mutation !! Gain-of-Function Mutation !! Translocation/Fusion
! Copy Number Loss !! Copy Number Gain !! LOH !! Loss-of-Function Mutation !! Gain-of-Function Mutation !! Translocation/Fusion
|-
|-
| EXAMPLE: X ||EXAMPLE: X || EXAMPLE: X || EXAMPLE: X || EXAMPLE: X || EXAMPLE: X
| || || || || X ||
|}
|}
==Internal Pages==
==Internal Pages==
==External Links==
==External Links==
'''[http://atlasgeneticsoncology.org/Genes/KITID127.html ''KIT'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
'''[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=kit ''KIT'' by COSMIC]''' - sequence information, expression, catalogue of mutations
'''[http://atlasgeneticsoncology.org/Genes/P53ID88.html ''TP53'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
'''[https://civicdb.org/events/genes/29/summary/variants/66/summary ''KIT'' by CIViC]''' - general knowledge and evidence-based variant specific information
'''[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=TP53 ''TP53'' by COSMIC]''' - sequence information, expression, catalogue of mutations
'''[https://pecan.stjude.cloud/proteinpaint/kit ''KIT'' by St. Jude ProteinPaint]''' mutational landscape and matched expression data.
'''[https://civicdb.org/events/genes/45/summary/variants/1300/summary ''TP53'' by CIViC]''' - general knowledge and evidence-based variant specific information
'''[https://pmkb.weill.cornell.edu/search?utf8=%E2%9C%93&search=kit ''KIT'' by Precision Medicine Knowledgebase (Weill Cornell)]''' - manually vetted interpretations of variants and CNVs
'''[http://p53.iarc.fr/ ''TP53'' by IARC]''' - ''TP53'' database with reference sequences and mutational landscape
'''[http://www.cancerindex.org/geneweb/KIT.htm ''KIT'' by Cancer Index]''' - gene, pathway, publication information matched to cancer type
'''[https://pecan.stjude.cloud/proteinpaint/tp53 ''TP53'' by St. Jude ProteinPaint]''' mutational landscape and matched expression data.
'''[http://oncokb.org/#/gene/kit ''KIT'' by OncoKB]''' - mutational landscape, mutation effect, variant classification
'''[https://pmkb.weill.cornell.edu/search?utf8=%E2%9C%93&search=tp53 ''TP53'' by Precision Medicine Knowledgebase (Weill Cornell)]''' - manually vetted interpretations of variants and CNVs
'''[https://www.mycancergenome.org/content/gene/kit/ ''KIT'' by My Cancer Genome]''' - brief gene overview
'''[http://www.cancerindex.org/geneweb/TP53.htm ''TP53'' by Cancer Index]''' - gene, pathway, publication information matched to cancer type
'''[http://www.uniprot.org/uniprot/P10721 ''KIT'' by UniProt]''' - protein and molecular structure and function
'''[http://oncokb.org/#/gene/TP53 ''TP53'' by OncoKB]''' - mutational landscape, mutation effect, variant classification
'''[http://pfam.xfam.org/protein/P10721 ''KIT'' by Pfam]''' - gene and protein structure and function information
'''[https://www.mycancergenome.org/content/gene/tp53/ ''TP53'' by My Cancer Genome]''' - brief gene overview
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=kit ''KIT'' by GeneCards]''' - general gene information and summaries
'''[http://www.uniprot.org/uniprot/P04637 ''TP53'' by UniProt]''' - protein and molecular structure and function
'''[https://www.ncbi.nlm.nih.gov/gene/3815 ''KIT'' by NCBI Gene]''' - general gene information and summaries
'''[https://pfam.xfam.org/family/p53 ''TP53'' by Pfam]''' - gene and protein structure and function information
'''[http://www.omim.org/entry/164920 ''KIT'' by OMIM]''' - compendium of human genes and genetic phenotypes
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=tp53 ''TP53'' by GeneCards]''' - general gene information and summaries
'''[https://databases.lovd.nl/shared/genes/kit ''KIT'' by LOVD(3)]''' - Leiden Open Variation Database
'''[https://www.ncbi.nlm.nih.gov/books/NBK1311/ GeneReviews]''' - information on Li Fraumeni Syndrome
'''[http://www.unav.es/genetica/TICdb/results.php?hgnc=kit ''KIT'' by TICdb]''' - database of Translocation breakpoints In Cancer
==References==
==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 ==
== Notes ==