Novel germline mutation of KIT associated with familial gastrointestinal stromal tumors and mastocytosis

Hartmann, Karin and Wardelmann, Eva and Ma, Yongsheng and Merkelbach-Bruse, Sabine and Preussner, Liane M. and Woolery, Carla and Baldus, Stephan E. and Heinicke, Thomas and Thiele, Juergen and Buettner, Reinhard and Longley, B. Jack. (2005) Novel germline mutation of KIT associated with familial gastrointestinal stromal tumors and mastocytosis. Gastroenterology, 129 (3). pp. 1042-1046.

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Official URL: https://edoc.unibas.ch/70835/

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Gastrointestinal stromal tumors (GISTs) are often associated with activating KIT mutations, affecting regulatory domains of the KIT tyrosine kinase. Sporadic mastocytosis in adults is usually also caused by KIT mutations that, however, activate KIT by affecting the intracellular enzymatic site of the molecule. Most GISTs respond to KIT inhibitors that bind to the enzymatic site; in most cases of mastocytosis, however, the modified enzymatic site is not affected by these drugs. We present a kindred with both familial GISTs and mastocytosis that express a novel germline KIT mutation in exon 8, resulting in deletion of codon 419 and affecting the extracellular domain of KIT. This mutation activates KIT, and the mutant KIT is inhibited by the tyrosine kinase inhibitor imatinib mesylate. Our studies identify a new regulatory region in the KIT molecule and strongly suggest that patients with extracellular KIT mutations respond to tyrosine kinase inhibitors.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Allergy and Immunity (Hartmann)
UniBasel Contributors:Hartmann, Karin
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Nov 2020 15:21
Deposited On:10 Nov 2020 15:21

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