Familial /sporadic gastrointestinal stromal tumors (GISTs)

Note	a recently described familial cancer syndrome characterized by development of multiple GISTs in different family members
Inheritance	autosomal dominant

Clinics

Phenotype and clinics

symptoms are attributable to development of benign and malignant GISTs hyperpigmentation and mast-cell disease may be associated etiology : GISTs originate from the CD34+/KIT+ interstitial cells of Cajal (ICCs) which development depends on the SCF/KIT interaction; germline/somatic KIT mutations in familial/solitary GISTs pathology : mesenchymal tumours developped in the gastrointestinal wall mainly characterized by positivity for both KIT and CD34; precursor tumour cells are likely ICCs that are located in and near the circular muscle layer of the stomach, small intestine and large intestine

Genes involved and Proteins

 

Gene Name	KIT
Location	4q12

DNA/RNA
Description	21 exons

Protein
Description	transmembrane SCF/MGF receptor with tyrosine kinase activity; binding of ligand (SCF) induces receptor dimerization, autophosphorylation and signal transduction via molecules containing SH2- domains

Mutations
Note	see diagram Gain-of-function mutations
Germinal	small deletion of one of two consecutive valine residues (codon 559 or 560, GTTGTT)
Somatic	simple in frame deletions, point mutations, deletion and point mutations are mainly clustered in exon 11 (from codon 550 to 584), but a few have been also identified in exon 9 and exon 13; all mutations are predicted to lead to constitutive phosphorylation and kinase activation the percentage of GISTs positive for c-kit mutations in exon 11 has been estimated to be 57% use of c-kit mutation as unfavourable prognostic marker is under debate

External links

GeneCards	KIT
GDB	KIT
OMIM	164920
HGMD	120117

Bibliography

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

Familial gastrointestinal stromal tumours with germline mutation of the KIT gene.

Nishida T, Hirota S, Taniguchi M, Hashimoto K, Isozaki K, Nakamura H, Kanakura Y, Tanaka T, Takabayashi A, Matsuda H, Kitamura Y

Nature genetics. 1998 ; 19 (4) : 323-324.

PMID 9697690

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

Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors.

Taniguchi M, Nishida T, Hirota S, Isozaki K, Ito T, Nomura T, Matsuda H, Kitamura Y

Cancer research. 1999 ; 59 (17) : 4297-4300.

PMID 10485475

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

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Contributor(s)

Written	09-1998	Lidia Larizza and Alessandro Beghini
		Medical Genetics, San Paolo School of Medicine, University of Milan Via A. di Rudini', 8, 20142 Milano, Italy
Updated	06-2000	Lidia Larizza and Alessandro Beghini
		Medical Genetics, San Paolo School of Medicine, University of Milan Via A. di Rudini', 8, 20142 Milano, Italy

Citation

This paper should be referenced as such :

Larizza L and Beghini A . Familial /sporadic gastrointestinal stromal tumors (GISTs). Atlas Genet Cytogenet Oncol Haematol. Septem ber 1998 . URL : http://AtlasGeneticsOncology.org/Genes/GastroISTID10029.html

Larizza L and Beghini A . Familial /sporadic gastrointestinal stromal tumors (GISTs). Atlas Genet Cytogenet Oncol Haematol. June 2000 . URL : http://AtlasGeneticsOncology.org/Genes/GastroISTID10029.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Sep 24 21:08:05 2008

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