title: Analysis of PTEN/MMAC1 alteration in neuroblastoma.
abstract: Neuroblastoma is the most common extracranial solid tumor in children. Although it has been reported that loss of heterozygosity at various loci, including 10q, frequently occurs in neuroblastoma, a bona fide tumor suppressor gene has not been identified. Recently, a gene mapped to chromosome 10q23, PTEN/MMAC1, was identified as a tumor suppressor gene that inhibits cell survival and cell proliferation by catalyzing the dephosphorylation of phosphatidylinositol 3,4,5-triphosphate. To screen for mutations of this gene in neuroblastoma, we analyzed 11 primary neuroblastoma tumors and 16 neuroblastoma cell lines for PTEN/MMAC1 mutations and deletions. All nine exons of the PTEN/MMAC1 gene were examined using the polymerase chain reaction-single strand conformational polymorphism assay and sequencing. Only one of the cell lines showed a mutation, a 1-bp frameshift deletion in exon 7, and an allelic loss in the opposite allele was revealed by a microsatellite analysis. Our results indicate that the disruption of the PTEN/MMAC1 gene is not a frequent event in neuroblastoma, and suggest that this disruption may be responsible for malignant progression in only a limited proportion of cases of neuroblastoma.
authors.affiliation: Department of Pediatrics, Miyazaki Medical College, 200 Kihara, Kiyotake-cho, 889-1692, Miyazaki, Japan. moritake@fc.miyazaki-med.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Moritake
authors.forename: Y
authors.initials: Y
authors.lastname: Horii
authors.forename: H
authors.initials: H
authors.lastname: Kuroda
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
mesh_terms: D000483:Alleles; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D018900:Dinucleotide Repeats; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D003062:Codon; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human