title: The KIT Exon 11 Stop Codon Mutation in Gastrointestinal Stromal Tumors: What Is the Clinical Meaning?
abstract: OBJECTIVE
  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.
authors: Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, Pisa University Hospital, University of Pisa, Pisa, Italy.
authors: Angela
authors: A
authors: Michelucci
authors: Caterina
authors: C
authors: Chiappetta
authors: Jessica
authors: J
authors: Cacciotti
authors: Norman
authors: N
authors: Veccia
authors: Elisa
authors: E
authors: Astri
authors: Martina
authors: M
authors: Leopizzi
authors: Romana
authors: R
authors: Prosperi Porta
authors: Vincenzo
authors: V
authors: Petrozza
authors: Carlo
authors: C
authors: Della Rocca
authors: Generoso
authors: G
authors: Bevilacqua
authors: Andrea
authors: A
authors: Cavazzana
authors: Claudio
authors: C
authors: Di Cristofano
keywords: Gastrointestinal stromal tumors; Platelet-derived growth factor alpha receptor; c-KIT