Gut Liver.
2013 Jan;7(1):35-40.
The KIT Exon 11 Stop Codon Mutation in Gastrointestinal Stromal Tumors: What Is the Clinical Meaning?
- Affiliations
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- 1Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, Pisa University Hospital, University of Pisa, Pisa, Italy. claudio.dicristofano@uniroma1.it
- 2Department of Medical Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
- 3Department of Oncology, Medical Oncology Unit, Pisa University Hospital, University of Pisa, Pisa, Italy.
- 4Surgical Pathology Unit, ASL1 Massa-Carrara, Tuscany, Italy.
Abstract
- BACKGROUND/AIMS
Gastrointestinal stromal tumors (GISTs) strongly express a receptor tyrosine kinase (RTK, c-KIT-CD117) harboring a KIT mutation that causes constitutive receptor activation leading to the development and growth of tumors; 35% of GISTs without KIT mutations have platelet-derived growth factor receptor alpha (PDGFRA) mutations, and the type of mutation plays an important role in the response to treatment. This study aimed to establish the frequency of stop codon mutations in the RTKs, KIT, and PDGFRA, in GISTs and correlate this molecular alteration with protein expression and treatment responsiveness.
METHODS
Seventy-nine GISTs were analyzed for both KIT and PDGFRA mutations. Immunohistochemical expression was studied in tissue microarray blocks.
RESULTS
We found three rare KIT mutations in exon 11 that induced a stop codon, two at position 563 and one at position 589, which have never been described before. All three tumors were CD117-, DOG1-, and CD34-positive. Two patients with a KIT stop codon mutation did not respond to imatinib therapy and died shortly after treatment.
CONCLUSIONS
The association between stop codon mutations in KIT and patient survival, if confirmed in a larger population, may be useful in choosing effective therapies.
MeSH Terms
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Benzamides
Codon, Terminator
Exons
Gastrointestinal Stromal Tumors
Growth and Development
Humans
Piperazines
Protein-Tyrosine Kinases
Pyrimidines
Receptor, Platelet-Derived Growth Factor alpha
Receptors, Platelet-Derived Growth Factor
Benzamides
Codon, Terminator
Piperazines
Protein-Tyrosine Kinases
Pyrimidines
Receptor, Platelet-Derived Growth Factor alpha
Receptors, Platelet-Derived Growth Factor
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