title: A novel K509I mutation of KIT identified in familial mastocytosis-in vitro and in vivo responsiveness to imatinib therapy.
abstract: KIT mutation has been implicated in sporadic mastocytosis, yet clusters in only a few sites in the molecule. For those malignancies associated with KIT mutation or over-expression, imatinib offers a specific therapeutic option, yet it has no effect on D816V mutation commonly seen in sporadic mastocytosis. The majority of cases of familial mastocytosis seem to lack KIT mutation. We report a kindred with mastocytosis in whom in vitro and in vivo sensitivity to imatinib was demonstrated. Mutation analysis of the KIT coding region in this family identified a novel A>T mutation at nucleotide 1547 [K509I] in exon 9 in both of the affected patients.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury, UK.
authors.forename: Ling Yan
authors.initials: LY
authors.lastname: Zhang
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Smith
authors.forename: Beate
authors.initials: B
authors.lastname: Schultheis
authors.forename: Jude
authors.initials: J
authors.lastname: Fitzgibbon
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Lister
authors.forename: Junia V
authors.initials: JV
authors.lastname: Melo
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.forename: Jamie D
authors.initials: JD
authors.lastname: Cavenagh
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D001549:Benzamides; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D000068877:Imatinib Mesylate; D008415:Mastocytosis / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D012326:RNA Splicing
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D017931:DNA Primers; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit