title: Mutational analysis of the tumour suppressor gene MMAC1/PTEN in malignant myeloid disorders.
abstract: The candidate tumour suppressor gene MMAC1/PTEN located at chromosome 10q23.3 has been reported to be frequently mutated in a number of solid tumours. Less is known about its status in leukaemia. In the present study we first analysed 13 leukaemia cell lines for mutations and homozygous deletions in MMAC1/PTEN using PCR and denaturing gradient gel electrophoresis (DGGE). We identified an intragenic deletion including MMAC1/PTEN exons 2-5 in an acute myelocytic leukaemia cell line, HL-60 blast, and an insertion of four nucleotides in exon 5 in an acute monocytic leukaemia cell line, U937. Analysis of 59 patients with acute myeloid leukaemia (AML), 26 patients with myelodysplastic syndromes (MDS) and 10 patients with chronic myeloid leukaemia (CML) only revealed a polymorphic base substitution in codon 44 in one AML patient, suggesting that mutations in the MMAC1/PTEN gene are infrequent genetic aberrations in myeloid leukaemia.
authors.affiliation: Department of Haematology, Aarhus University Hospital, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Aggerholm
authors.forename: K
authors.initials: K
authors.lastname: Grønbaek
authors.forename: P
authors.initials: P
authors.lastname: Guldberg
authors.forename: P
authors.initials: P
authors.lastname: Hokland
mesh_terms: D000208:Acute Disease; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D018922:HL-60 Cells; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics*; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D020298:U937 Cells
chemical_list: D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human