Document Type: Research Articles
Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Diagnostic Genomic Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar.
King Faisal Cancer Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
Department of Pathology, King Abdulaziz Medical City, Jeddah, Saudi Arabia.
Department of Pediatrics, University of Toronto, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Canada.
Genomics, Ontario Institute for Cancer Research, Toronto, Canada.
Background: Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal
tract, which originate from the interstitial cells of Cajal. These tumors are characterized by expression of CD117 and
CD34 antigens and activating mutations in the KIT and PDGFRA genes. While KIT and PDGFRA mutations have been
extensively studied in other populations, the spectrum of mutations in Arab patients remains unknown. The study aimed
at determining the distribution of KIT and PDGFRA mutations and phenotypic characterization of the gastrointestinal
stromal tumors in Arab patients. Methods: Sanger sequencing was used to analyze 52 archived gastrointestinal stromal
tumors for mutations in the KIT and the PDGFRA genes. Tumor descriptions were obtained from the clinical reports
of patients. Results: In these patients, most tumors occur in the stomach, followed by the rest of the digestive tract. A
vast majority of tumors express the CD117 and CD34 antigens. Sequencing of the KIT and PDGFRA genes identified
five non-synonymous mutations and 26 deletions (25 novel) in exon 11 of the KIT gene. All non-synonymous mutations
and deletions affect the juxta-membrane domain, which is known to inhibit ligand-independent activation of the KIT
receptor. No mutations were found in the PDGFRA gene. Conclusions: Molecular profiling of the gastrointestinal
stromal tumors in Arab patients identified a unique spectrum of mutations in exon 11 of the KIT gene. These data are
important for the diagnosis and management of patients of Arab ethnic origin.