The KIT Exon 11 Stop Codon Mutation in Gastrointestinal Stromal Tumors: What Is the Clinical Meaning?

Abstract

Background/AimsGastrointestinal 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.MethodsSeventy-nine GISTs were analyzed for both KIT and PDGFRA mutations. Immunohistochemical expression was studied in tissue microarray blocks.ResultsWe 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.ConclusionsThe association between stop codon mutations in KIT and patient survival, if confirmed in a larger population, may be useful in choosing effective therapies.

Ileal Gastrointestinal Stromal Tumor as a Rare Cause of Gastrointestinal Bleed: A Case Report and Brief Review of the Literature

“…ICCs (which express cKIT and DOG1 and variably express CD34) have recently been identified as pacemaker cells for gastrointestinal motor activity, initiating and maintaining peristalsis [ 4 , 5 ]. Prognosis depends on tumor size, mitotic rate, and site of origin [ 6 ].…”