title: Mutational analysis of class III receptor tyrosine kinases (C-KIT, C-FMS, FLT3) in idiopathic myelofibrosis.
abstract: Genomic DNA from patients with idiopathic myelofibrosis (IMF) was screened by polymerase chain reaction (PCR) and conformation sensitive gel electrophoresis (CSGE) for mutations in the C-KIT gene (60 patients), as well as the C-FMS and FLT3 genes (40 patients). Intronic primers were used to amplify the entire coding region of both the C-KIT and C-FMS genes, and selected regions of the FLT3 gene. CSGE and direct DNA sequencing detected all previously reported as well as several novel polymorphisms in each of the genes. A novel c-fms exon 9 mutation (Gly413Ser) was detected in two patients. Its functional significance remains to be determined. The c-kit mutation Asp52Asn, previously described in two of six IMF patients in Japan, was not detected in this study. In addition, the reported c-fms mutations involving codons 301 and 969 were not identified. Therefore, in contrast to acute myeloid leukaemia, mutations in RTKs class III do not appear to play a significant pathogenetic role in idiopathic myelofibrosis.
authors.affiliation: Academic Unit of Haematology, Division of Genomic Medicine, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: Faisel M
authors.initials: FM
authors.lastname: Abu-Duhier
authors.forename: Anne C
authors.initials: AC
authors.lastname: Goodeve
authors.forename: Rory S
authors.initials: RS
authors.lastname: Care
authors.forename: Mamdooh
authors.initials: M
authors.lastname: Gari
authors.forename: Gill A
authors.initials: GA
authors.lastname: Wilson
authors.forename: Ian R
authors.initials: IR
authors.lastname: Peake
authors.forename: John T
authors.initials: JT
authors.lastname: Reilly
mesh_terms: D004252:DNA Mutational Analysis; D016236:Genes, fms; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D055728:Primary Myelofibrosis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3
chemical_list: D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3