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Open Access 01-12-2015 | Research article

KIT exon 10 variant (c.1621 A > C) single nucleotide polymorphism as predictor of GIST patient outcome

Authors: Mehdi Brahmi, Laurent Alberti, Armelle Dufresne, Isabelle Ray-Coquard, Philippe Cassier, Pierre Meeus, Anne-Valérie Decouvelaere, Dominique Ranchère-Vince, Jean-Yves Blay

Published in: BMC Cancer | Issue 1/2015

Abstract

Background

Tumor genotype plays a crucial role in clinical management of GIST. Whether genetic polymorphism of KIT may influence GIST patient outcome is unclear.

Methods

We investigated the biological and clinical significance of the presence of KIT 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, KIT^L541 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 %) harboured KIT^L541, similarly to the control group of healthy donors (n = 10 of 60, 17 %). A higher prevalence of the variant KIT^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 with KIT^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 in KIT^L541 and KIT^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.

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Title: KIT exon 10 variant (c.1621 A > C) single nucleotide polymorphism as predictor of GIST patient outcome
Authors: Mehdi Brahmi
Laurent Alberti
Armelle Dufresne
Isabelle Ray-Coquard
Philippe Cassier
Pierre Meeus
Anne-Valérie Decouvelaere
Dominique Ranchère-Vince
Jean-Yves Blay
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-015-1817-5

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Abstract

Background

Methods

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