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.
journal_name
BMC Cancerjournal_title
BMC cancerauthors
Brahmi M,Alberti L,Dufresne A,Ray-Coquard I,Cassier P,Meeus P,Decouvelaere AV,Ranchère-Vince D,Blay JYdoi
10.1186/s12885-015-1817-5subject
Has Abstractpub_date
2015-10-24 00:00:00pages
780issn
1471-2407pii
10.1186/s12885-015-1817-5journal_volume
15pub_type
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