title: Driver KIT mutations in melanoma cluster in four hotspots.
abstract: There has been a great deal of interest in understanding the role of KIT in melanoma since the discovery of KIT mutations in a subset of melanoma. Although a significant proportion of these melanomas respond to KIT inhibitors, the presence of a KIT mutation does not guarantee a response to KIT inhibitors. Because recent data seem to indicate that only melanoma with specific KIT mutations respond to KIT inhibitors, we investigated which KIT mutations are driver mutations in melanoma and are therefore therapeutically relevant. We established that 70% of KIT mutations in melanoma are located in four hotspots (L576, K642, W557-V560, and D816-A829) and that these mutations are oncogenic in melanocytes and are bona-fide driver mutations. Testing for KIT mutations should therefore concentrate on these four hotspots, which can be targeted therapeutically.
authors.affiliation: aINSERM, U976, Skin Research Institute, Hôpital Saint Louis bUniversité Paris Diderot, Sorbonne Paris Cité cDermatology Department dPharmacology Department, AP-HP, Hôpital Saint Louis, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dumaz
authors.forename: Jocelyne
authors.initials: J
authors.lastname: André
authors.forename: Aurélie
authors.initials: A
authors.lastname: Sadoux
authors.forename: Florence
authors.initials: F
authors.lastname: Laugier
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Podgorniak
authors.forename: Samia
authors.initials: S
authors.lastname: Mourah
authors.forename: Céleste
authors.initials: C
authors.lastname: Lebbé
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009362:Neoplasm Metastasis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D019009:Proto-Oncogene Proteins c-kit