Atlas of Genetics and Cytogenetics in Oncology and Haematology
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KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog)
| Identity |
| Other names | SCFR (Stem Cell Factor Receptor) |
| CD117 | |
| HGNC (Hugo) | KIT |
| LocusID (NCBI) | 3815 |
| Location | 4q12 |
| Location_base_pair | Starts at 55524095 and ends at 55606881 bp from pter ( according to hg19-Feb_2009) [Mapping] |
| Local_order | centromere-PDGFRA -KIT-KDR-telomere |
 | |
| KIT (4q12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. | |
| DNA/RNA |
| Description | spans 89 kb; 21 exons; size of intron 1 : 37,4 kb |
| Transcription | 5,23 kb mRNA; alternative splicing of exon 9 gives rise to two isoforms, KitA and Kit, that differ by the presence or absence of four aminoacids. |
| Protein |
| Description | 976 aa; 145 kDa; type III receptor tyrosine kinase; contains an extracellular domains with 5 Ig-like loops, a highly hydrophobic transmenbrane domain (23 aa), and an intracellular domain with tyrosine kinase activity split by a kinase insert (KI) in an ATP-binding region and in the phosphotransferase domain |
| Expression | hematopoietic stem cells, mast cells, melanocytes, germ-cell lineages and ICCs (Interstitial cells of Cajal). |
| Localisation | plasma membrane |
| Function | SCF/MGF receptor with tyrosine kinase activity; binding of ligand (SCF) induces receptor dimerization, autophosphorylation and signal transduction via molecules containing SH2- domains. |
 | |
| Homology | with CSF-1R, PDGFRb, PDGFRa, and FLT3. |
| Mutations |
| Note | see diagrams: Loss-of-function mutations, and Gain-of-function mutations |
 | |
| Germinal | in piebaldism, and in familial gastrointestinal stromal tumours (see below). |
| Somatic | in aggressive mastocytosis, mast cell leukemia, ANLL with/without mast cell involvement, myeloproliferative disorders, colon carcinoma and gastrointestinal stromal tumours and germ cell tumors (GCCs) |
| Implicated in |
| Entity | Piebaldism. |
| Disease | autosomal dominant disorder of pigmentation; loss of function abnormalities of the c-kit gene have been demonstrated in 59% of the typical patients. |
| Entity | Familial gastrointestinal stromal tumours and sporadic gastrointestinal stromal tumours (GISTs). |
| Disease | GISTs are the most common mesenchymal tumors in the human digestive tract; they originate from kit-expressing cells (ICCs), and often have activating c-kit mutations clustered in the juxtamembrane domain. |
| Entity | systemic mast cell disease (SMCD) |
| Disease | mast cell hyperplasia in the bone marrow, liver, spleen, lymph nodes, gastrointestinal tract and skin; gain of function mutations are detected in most patients |
| Prognosis | depending on the four clinical entities recognized: indolent form, form associated with hematologic disorder, aggressive SMCD and mast cell leukemia; leukemic transformation with mast cell involvement is characterized by rapid progression of disease with a survival time less than 1 year |
| Oncogenesis | clinical features of malignant hematopoietic cell growth are influenced by the time, the location of c-kit mutative events, and the number of associated lesions. |
| Entity | Core binding factor leukemias (ANLL-M2 with t(8;21) (link), (ANLL-M4Eo with inv(16)) |
| Disease | characterized by disruption and loss of CBFa2/AML1 - CBFb/PEBP2b function. Myelomonoblastic leukemia cells are marked by combined positivity for the stem cell antigens CD34, CD117 and high frequency of c-kit mutations ( see Figure on CBF leukemia and KIT mutations) |
| To be noted |
| loss of expression of c-KIT appears to be associated with progression of some tumors (melanoma) and autocrine/paracrine stimulation of the c-kit/SCF system may participate in human solid tumors such as lung, breast, testicular and gynecological malignancies. |
| Other Leukemias implicated (Data extracted from papers in the Atlas) |
| Leukemias | 11q23ChildAMLID1615 | 11q23ID1030 | 11q23secondLeukID1131 | t1119ELLID1029 |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) |
| Solid Tumors | AmeloblastomID5945 | MedulloblastomaID5065 | rhabID5004 | bladID5001 |
| External links |
| Bibliography |
| Cloning and structural analysis of the human c-kit gene. |
| Vandenbark GR, deCastro CM, Taylor H, Dew-Knight S, Kaufman RE |
| Oncogene. 1992 ; 7 (7) : 1259-1266. |
| PMID 1377810 |
| Novel mutations and deletions of the KIT (steel factor receptor) gene in human piebaldism. |
| Ezoe K, Holmes SA, Ho L, Bennett CP, Bolognia JL, Brueton L, Burn J, Falabella R, Gatto EM, Ishii N |
| American journal of human genetics. 1995 ; 56 (1) : 58-66. |
| PMID 7529964 |
| Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm. |
| Longley BJ, Tyrrell L, Lu SZ, Ma YS, Langley K, Ding TG, Duffy T, Jacobs P, Tang LH, Modlin I |
| Nature genetics. 1996 ; 12 (3) : 312-314. |
| PMID 8589724 |
| Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes. |
| Andre C, Hampe A, Lachaume P, Martin E, Wang XP, Manus V, Hu WX, Galibert F |
| Genomics. 1997 ; 39 (2) : 216-226. |
| PMID 9027509 |
| Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. |
| Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y |
| Science (New York, N.Y.). 1998 ; 279 (5350) : 577-580. |
| PMID 9438854 |
| C-kit gene abnormalities in gastrointestinal stromal tumors (tumors of interstitial cells of Cajal. |
| Sakurai S, Fukasawa T, Chong JM, Tanaka A, Fukayama M |
| Japanese journal of cancer research : Gann. 1999 ; 90 (12) : 1321-1328. |
| PMID 10665649 |
| c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia. |
| Gari M, Goodeve A, Wilson G, Winship P, Langabeer S, Linch D, Vandenberghe E, Peake I, Reilly J |
| British journal of haematology. 1999 ; 105 (4) : 894-900. |
| PMID 10554798 |
| Activating c-kit gene mutations in human germ cell tumors. |
| Tian Q, Frierson HF Jr, Krystal GW, Moskaluk CA |
| The American journal of pathology. 1999 ; 154 (6) : 1643-1647. |
| PMID 10362788 |
| Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. |
| Longley BJ Jr, Metcalfe DD, Tharp M, Wang X, Tyrrell L, Lu SZ, Heitjan D, Ma Y |
| Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (4) : 1609-1614. |
| PMID 9990072 |
| KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. |
| Lux ML, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri G, Xiao S, Singer S, Fletcher CD, Fletcher JA |
| The American journal of pathology. 2000 ; 156 (3) : 791-795. |
| PMID 10702394 |
| C-kit mutations in core binding factor leukemias. |
| Beghini A, Peterlongo P, Ripamonti CB, Larizza L, Cairoli R, Morra E, Mecucci C |
| Blood. 2000 ; 95 (2) : 726-727. |
| PMID 10660321 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 09-1998 | Lidia Larizza and Alessandro Beghini |
| Updated | 06-2000 | Lidia Larizza and Alessandro Beghini |
| Citation |
| This paper should be referenced as such : |
| Larizza, L ; Beghini, A |
| KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) |
| Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):96-98. |
| Free journal version : [ pdf ] [ DOI ] |
| History of this paper: |
| Larizza, L ; Beghini, A. KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog). Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):96-98. |
| http://documents.irevues.inist.fr/bitstream/2042/37632/1/06-2000-KITID127.pdf |
| URL : http://AtlasGeneticsOncology.org/Genes/KITID127.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Tue Feb 17 20:29:05 CET 2015 |
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