KIT exon 10 variant (c.1621 A > C) single nucleotide polymorphism as predictor of GIST patient outcome. Issue 1 (December 2015) - Brahmi, Mehdi
Abstract Background Tumor genotype plays a crucial role in clinical management of GIST. Whether genetic polymorphism ofKIT may influence GIST patient outcome is unclear. Methods We investigated the biological and clinical significance of the presence ofKIT exon 10 variant (c.1621 A > C), KIT L541, in a transfected cell line (3 T3 L541) and in two retrospectively collected series of 109 GIST patients in total. The control group consisted of 60 healthy donors collected at the French department of blood transfusion. Results In the 3 T3 L541 cell line, KITL541 protein exhibited a spontaneous phosphorylation status comparable to that of wild-type KIT but displayed a phosphorylation pattern of AKT and ERK1/2 that was found similar to that of the classical mutated forms of the KIT receptor. Of 109 patients enrolled in this retrospective translational research study, 24 (22 %) harbouredKIT L541, similarly to the control group of healthy donors (n = 10 of 60, 17 %). A higher prevalence of the variantKIT L541 was observed in patients with metastatic status at diagnosis (KIT L541 correlated nine of 22 versus 15 of 87, p = 0.02). In addition, patients withKIT L541 and localized GIST had a higher rate of relapse at 5 years and lower relapse free survival at 5 years in univariate, as well as in multivariate analysis. Response rate and duration of response to imatinib was similar inKIT L541 andKIT M541 patients. Conclusion KIT L541 genotype is associated with a higher risk of metastasis at diagnosis and a higher risk of relapse in GIST patients.