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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]).
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/Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]
[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)
GIST (gastrointestinal stromal tumors)
Mast cell disease
Melanoma
[http://www.ccga.io/index.php/Melanoma_skin_Cancer Melanoma Skin Cancer]
[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. Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous leukemia, and piebaldism. The Kit protein plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. ([https://www.uniprot.org/uniprot/P10721 adapted from UniProt Description]).
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 occuring at postion D816juxtamembrane domain, and the XX doamin and The most common mutations found in KIT occur in the Tyrosine Kinase domain, with the vast majority being at the D816 residue ([https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=kit see COSMIC]).
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
'''[http://atlasgeneticsoncology.org/Genes/KITID127.html ''KIT'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
3. Rubin B.P et al. (2001). KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res. 61: 8118-21. PMID: 11719439
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 ==