Spectrum of the KIT Gene Mutations in Gastrointestinal Stromal Tumors in Arab Patients

Abstract

Background: Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal<br />tract, which originate from the interstitial cells of Cajal. These tumors are characterized by expression of CD117 and<br />CD34 antigens and activating mutations in the KIT and PDGFRA genes. While KIT and PDGFRA mutations have been<br />extensively studied in other populations, the spectrum of mutations in Arab patients remains unknown. The study aimed<br />at determining the distribution of KIT and PDGFRA mutations and phenotypic characterization of the gastrointestinal<br />stromal tumors in Arab patients. Methods: Sanger sequencing was used to analyze 52 archived gastrointestinal stromal<br />tumors for mutations in the KIT and the PDGFRA genes. Tumor descriptions were obtained from the clinical reports<br />of patients. Results: In these patients, most tumors occur in the stomach, followed by the rest of the digestive tract. A<br />vast majority of tumors express the CD117 and CD34 antigens. Sequencing of the KIT and PDGFRA genes identified<br />five non-synonymous mutations and 26 deletions (25 novel) in exon 11 of the KIT gene. All non-synonymous mutations<br />and deletions affect the juxta-membrane domain, which is known to inhibit ligand-independent activation of the KIT<br />receptor. No mutations were found in the PDGFRA gene. Conclusions: Molecular profiling of the gastrointestinal<br />stromal tumors in Arab patients identified a unique spectrum of mutations in exon 11 of the KIT gene. These data are<br />important for the diagnosis and management of patients of Arab ethnic origin.