title: FMS mutations in patients following cytotoxic therapy for lymphoma.
abstract: Point mutations at codons 301 and 969 of the FMS proto-oncogene have been reported in both myelodysplasia (MDS) and acute myeloid leukaemia (AML). We report here the incidence of such mutations in patients at risk of developing secondary MDS and AML. Peripheral blood DNA from 70 patients in remission from lymphoma was screened for mutations by oligonucleotide (ONH) using mutant specific probes. Codon 969 mutations were detected in 11 of the 70 (15.7%) cases. No codon 301 mutations were detected. Five of these mutations were confirmed using an independent technique (single nucleotide primer extension analysis, SNPE) and a further mutation was detected in a single patient using single-stranded conformational polymorphism analysis (SSCP). No codon 969 mutations were detected in 62 lymphoma biopsy specimens from these patients or from three patients with detectable FMS mutations where pre-therapy marrow was investigated by ONH. No mutations at either codons 301 or 969 were detected by ONH in 61 normal controls. Somatic mutations at codon 969 of the FMS gene occur commonly following cytotoxic therapy for lymphoma and their detection indicates the presence of a clonally expanded population of abnormal cells.
authors.affiliation: Department of Haematology, University of Wales College of Medicine, Health Park, Cardiff, U.K.
authors.forename: A
authors.initials: A
authors.lastname: Baker
authors.forename: P
authors.initials: P
authors.lastname: Cachia
authors.forename: S
authors.initials: S
authors.lastname: Ridge
authors.forename: H
authors.initials: H
authors.lastname: McGlynn
authors.forename: R
authors.initials: R
authors.lastname: Clarke
authors.forename: J
authors.initials: J
authors.lastname: Whittaker
authors.forename: A
authors.initials: A
authors.lastname: Jacobs
authors.forename: R A
authors.initials: RA
authors.lastname: Padua
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001483:Base Sequence; D003603:Cytotoxins / Q000009:adverse effects; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D016236:Genes, fms; D011905:Genes, ras; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D017931:DNA Primers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas