Annotation Detail

Information
Associated Genes
KIT
Associated Variants
KIT p.Asp580del (p.D580del) ( ENST00000412167.7, ENST00000288135.6, ENST00000686011.1, ENST00000687109.1, ENST00000687246.1, ENST00000687295.1, ENST00000689832.1, ENST00000689994.1, ENST00000690543.1, ENST00000692783.1 )
KIT p.Asp580del (p.D580del) ( ENST00000288135.6, ENST00000412167.7, ENST00000686011.1, ENST00000687109.1, ENST00000687246.1, ENST00000687295.1, ENST00000689832.1, ENST00000689994.1, ENST00000690543.1, ENST00000692783.1 )
Associated Disease
gastrointestinal stromal tumor
Source Database
CIViC Evidence
Description
This prospective study of 127 patients with metastatic gastrointestinal stromal tumors (GISTs) examined the relationship between kinase (KIT and PDGFRA) genotype and treatment outcome for patients enrolled in a randomized phase II trial of imatinib (CSTI571B 2222). Six GISTs harbored PDGFRA mutations, three of which were deemed imatinib-sensitive by the authors: 1 DIMH842-845 deletion, one I843 deletion, and one V561D point mutation. Two of these patients' GISTs experienced partial responses to imatinib and one experienced progressive disease. Overall, the partial response rate of patients with an imatinib sensitive mutation of KIT or PDGFRA was 75.7% (87 of 115 patients), whereas the partial response rate in patients with no kinase mutation or a previously described imatinib resistant mutation was 0% (0 of 12 patients). The authors concluded that PDGFRA gain-of-function mutations may account for imatinib sensivity in some WT KIT GISTs.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/2487
Gene URL
https://civic.genome.wustl.edu/links/genes/29
Variant URL
https://civic.genome.wustl.edu/links/variants/977
Rating
3
Evidence Type
Predictive
Disease
Gastrointestinal Stromal Tumor
Evidence Direction
Supports
Drug
Imatinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
14645423
Drugs
Drug NameSensitivitySupported
ImatinibSensitivitytrue