title: Mutations within the FLR exon of NF1 are rare in myelodysplastic syndromes and acute myelocytic leukemias.
abstract: A mutational hotspot in the neurofibromatosis 1 (NF1) gene has recently emerged from the analysis of different malignancies including one patient with myelodysplastic syndrome (MDS). In these cases, Lys 1423 in the GTPase-activating protein (GAP)-related domain of NF1 is substituted which causes a significant reduction of intrinsic GAP activity. We studied 57 MDS patients and 27 cases of acute myelocytic leukemia (AML) for mutations at codon 1423 in the so-called FLR exon of NF1 by an assay based on restriction enzyme digestion. We investigated the entire FLR exon and its flanking intron sequences using single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products and sequencing. None of the cases exhibited a codon 1423 mutation. However, a patient with chronic myelomonocytic leukemia (CMML) showed a 3 bp deletion within the splice acceptor region in front of the FLR exon. These data suggest that NF1 exon FLR mutations contribute infrequently to the development of MDS and AML.
authors.affiliation: Department of Pediatrics II, University of Ulm, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Ludwig
authors.forename: J W
authors.initials: JW
authors.lastname: Janssen
authors.forename: A S
authors.initials: AS
authors.lastname: Schulz
authors.forename: C R
authors.initials: CR
authors.lastname: Bartram
mesh_terms: D000208:Acute Disease; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000235:genetics; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry
chemical_list: D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides