KIT mutations are common in testicular seminomas.

摘要: Expression of KIT tyrosine kinase is critical for normal germ cell development and observed in the majority seminomas. Activating mutations are common gastrointestinal stromal tumors mastocytosis. In this study we examined frequency spectrum 54 testicular seminomas, 1 ovarian dysgerminoma 37 non-seminomatous (NSGCT). Fourteen seminomas (25.9%) contained exon 17 point including D816V (6 cases), D816H (3 Y823D (2 single examples Y823C, N822K, T801I. No were found or NSGCTs. transient transfection assays, mutant isoforms D816V, D816H, Y823D, N822K constitutively phosphorylated absence natural ligand KIT, stem factor (SCF). contrast, activation T801I wild-type required SCF. Mutants inhibited by imatinib mesylate (Gleevec, previously STI571) whereas both resistant to mesylate. Biochemical evidence activation, as assessed phosphorylation association with phosphatidylinositol (PI) 3-kinase tumor lysates, was largely confined a genomic mutation. These findings suggest that activating may contribute tumorigenesis subset but not involved NSGCT.