Extracellular domain c-kit mutation with duplication of Ser501Ala502 found in gastrointestinal stromal tumors is more imatinib- and nilotinib-sensitive than that with duplication of Ala502Tyr503.

摘要: The great majority of gastrointestinal stromal tumors (GISTs) have gain-of-function mutations the c-kit gene, which encodes KIT receptor tyrosine kinase. Most are located at exon 11, but some 9 or other exons. Mutation types 11 vary, while most a particular duplication Ala502Tyr503 (KIT-Dup-Ala502Tyr503). Recently Ser501Ala502 (KIT-Dup-Ser501Ala502) has been reported in two cases pediatric mastocytosis and one case adult mast cell leukemia. Although KIT-Dup-Ser501Ala502 had not GISTs, we found GIST possessing mutation 45 with gene mutations, among total approximately 500 examined. In this report, briefly summarize clinicopathological findings cases, characterize biology mutation. When autophosphorylation was examined by transient transfection cDNA Dup-Ser501Ala502 into CHO-K1 cells, ligand-independently activating. inhibitory effect selective kinase inhibitors, imatinib nilotinib, on compared that KIT-Dup-Ala502Tyr503. Imatinib efficiently inhibited constitutive activation concentration 0.1 μM, whereas it KIT-Dup-Ala502Tyr503 10 μM. Constitutive KIT-Dup-Ser502Ala503 nilotinib even 10 μM KIT-Dup-Ala501Tyr502 almost completely 1 μM. results suggest could be more effective GISTs than those fact, patient showed long-term stable disease administration usual dose 400 mg imatinib. sites closely located, imatinib- nilotinib-sensitive distinguishable from