The KIT Exon 11 Stop Codon Mutation in Gastrointestinal Stromal Tumors: What Is the Clinical Meaning?.
- Author:
Angela MICHELUCCI
1
;
Caterina CHIAPPETTA
;
Jessica CACCIOTTI
;
Norman VECCIA
;
Elisa ASTRI
;
Martina LEOPIZZI
;
Romana PROSPERI PORTA
;
Vincenzo PETROZZA
;
Carlo DELLA ROCCA
;
Generoso BEVILACQUA
;
Andrea CAVAZZANA
;
Claudio DI CRISTOFANO
Author Information
1. Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, Pisa University Hospital, University of Pisa, Pisa, Italy. claudio.dicristofano@uniroma1.it
- Publication Type:Original Article
- Keywords:
Gastrointestinal stromal tumors;
c-KIT;
Platelet-derived growth factor alpha receptor
- MeSH:
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
- From:Gut and Liver
2013;7(1):35-40
- CountryRepublic of Korea
- Language:English
-
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.
