title: Tumour heterogeneity of mucosal melanomas during treatment with imatinib.
abstract: A comparison of in vitro and in vivo characteristics of tumour cells derived from patients with mucosal melanoma treated with imatinib was performed with respect to KIT mutations. Three patients with mucosal melanoma were treated with imatinib. Patient-derived tumour material was used to establish melanoma cell cultures ex vivo. We evaluated tumour material and cell cultures for KIT protein expression and KIT mutation status. In addition, proliferation assays with melanoma cell cultures were performed with imatinib. Expression of KIT protein and KIT mutation was shown in two patients who responded to imatinib in vivo. Cells derived from a third patient who did not respond to imatinib did not express KIT and lacked a KIT mutation. Patient-derived melanoma cells did not show any KIT mutations, nor did they respond to imatinib in vitro. Our study underlines that melanoma consists of a heterogeneous cell population, making it imperative to use the mapping of involved activating tumour growth-driving pathways in order to improve response to therapy with kinase inhibitors.
authors.affiliation: Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: N L
authors.initials: NL
authors.lastname: Schoenewolf
authors.forename: M
authors.initials: M
authors.lastname: Urosevic-Maiwald
authors.forename: R
authors.initials: R
authors.lastname: Dummer
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000188:drug therapy / Q000235:genetics; D001549:Benzamides; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014846:Vulvar Neoplasms / Q000188:drug therapy / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit