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Characterization of S628N: a novel KIT mutation found in a metastatic melanoma

Abstract : IMPORTANCE: The KIT receptor is mutated in approximately 15% of acral, mucosal, and chronic, sun-damaged melanomas. The status of KIT mutations is of interest because they usually are mutually exclusive with N-RAS and B-RAF mutations and because of the availability of KIT kinase inhibitors in the clinic. Some recurrent KIT mutations are well characterized; others are poorly described. OBSERVATIONS: We describe a novel KIT mutation in a patient with metastatic melanoma. The mutation, located in exon 13, resulted in S628N substitution in the KIT receptor. Using all-atom molecular dynamics simulations, biochemical assays, and cell-based assays, we showed that the mutation is a bona fide gain-of-function oncogenic mutation. Furthermore,we evaluated the sensitivity of the mutant to imatinib and dasatinib. CONCLUSIONS AND RELEVANCE: We report a novel KIT gain-of-function mutation with S628N substitution (exon 13) and show that it is sensitive to imatinib in vitro. Therefore, patients with this mutation may be eligible for KIT kinase inhibitor–based therapy. Further studies are needed to evaluate the clinical benefit of such therapy.
Keywords : KIT S628N melanoma
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Contributor : Isaure Chauvot de Beauchene <>
Submitted on : Friday, November 16, 2018 - 2:37:07 PM
Last modification on : Wednesday, August 7, 2019 - 5:26:03 PM

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Marina Vita, Julie Tisserand, Isaure Chauvot de Beauchêne, Nicolas Panel, Luba Tchertanov, et al.. Characterization of S628N: a novel KIT mutation found in a metastatic melanoma. JAMA Dermatology, American Medical Association, 2014, 150 (12), ⟨10.1001/jamadermatol.2014.1437⟩. ⟨hal-01505849⟩



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