title: Molecular analysis of PTEN and MXI1 in primary bladder carcinoma.
abstract: Loss of heterozygosity (LOH) on 10q is associated with late-stage events in urothelial neoplastic progression. The tumor suppressor gene PTEN, which is mutated or homozygously deleted in numerous cancers, maps to a region of 10q within the reported region of minimal loss in bladder tumors. In two recent studies alterations in the PTEN gene occur at a low frequency in bladder tumors displaying 10q LOH. We have screened 35 late-stage bladder tumors for mutations in PTEN and MXI1, both genes mapping to chromosome 10q. Using single-strand conformation polymorphism analysis, we identified 6 tumors harboring mutations in PTEN and 2 additional tumors displaying homozygous deletion at this locus. No MXI1 mutations were identified within the same tumor panel. Of 16 bladder tumor cell lines analyzed, 2 showed homozygous deletion of PTEN and 3 harbored point mutations resulting in an amino acid change. Two cell lines harbored missense mutations in MXI1. We report a significantly higher frequency of PTEN alterations in bladder carcinoma (23%) than was previously recorded, with no accompanying mutations in the MXI1 gene.
authors.affiliation: Department of Urology, Lahey Clinic, Burlington, MA, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Rieger-Christ
authors.forename: J M
authors.initials: JM
authors.lastname: Latini
authors.forename: A
authors.initials: A
authors.lastname: Moinzadeh
authors.forename: J
authors.initials: J
authors.lastname: Stoffel
authors.forename: J A
authors.initials: JA
authors.lastname: Pezza
authors.forename: K
authors.initials: K
authors.lastname: Saini
authors.forename: J A
authors.initials: JA
authors.lastname: Libertino
authors.forename: I C
authors.initials: IC
authors.lastname: Summerhayes
mesh_terms: D019943:Amino Acid Substitution; D051792:Basic Helix-Loop-Helix Proteins; D001943:Breast Neoplasms; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008297:Male; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011471:Prostatic Neoplasms; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C079440:MXI1 protein, human; C494929:PTEN protein, human