title: Mutation analysis of the PTEN/MMAC1 gene in lung cancer.
abstract: We studied PTEN/MMAC1, a newly discovered candidate tumor suppressor gene at 10q23.3, for mutations in lung cancer. One hundred and thirty-six lung cancer cell line DNAs (66 small cell lung cancers, SCLC, 61 non-small cell lung cancers, NSCLC, four mesotheliomas, five extrapulmonary small cell cancers) were analysed for PTEN/MMAC1 homozygous deletions and five (8%) SCLC lines showed homozygous deletions interrupting the PTEN/MMAC1 gene. Using single stranded conformation polymorphism (SSCP) analysis, we screened the PTEN/MMAC1 open reading frame of 53 lung cancer cell line cDNAs for point mutations and found that 3/35 SCLCs and 3/18 NSCLCs contained homozygous amino acid sequence altering mutations. Northern blot analysis revealed that expression of the PTEN/MMAC1 gene was considerably lower in all the tumor cell lines with point mutations while no expression was detected for cell lines with PTEN/MMAC1 homozygous deletions. Mutation analysis of 22 uncultured, microdissected, primary SCLC tumors and metastases showed two silent mutations, and two apparent homozygous deletions. We also discovered a processed pseudogene (PTEN2) which has 98.5% nt identity to PTEN/MMAC1, that needs to be accounted for in cDNA mutation analysis. Our findings suggest that genetic abnormalities of the PTEN/MMAC1 gene are only involved in a relatively small subset of lung cancers.
authors.affiliation: Hamon Center for Therapeutic Oncology Research, University of Texas, Southwestern Medical Center, Dallas 75235, USA.
authors.forename: E
authors.initials: E
authors.lastname: Forgacs
authors.forename: E J
authors.initials: EJ
authors.lastname: Biesterveld
authors.forename: Y
authors.initials: Y
authors.lastname: Sekido
authors.forename: K
authors.initials: K
authors.lastname: Fong
authors.forename: S
authors.initials: S
authors.lastname: Muneer
authors.forename: I I
authors.initials: II
authors.lastname: Wistuba
authors.forename: S
authors.initials: S
authors.lastname: Milchgrub
authors.forename: R
authors.initials: R
authors.lastname: Brezinschek
authors.forename: A
authors.initials: A
authors.lastname: Virmani
authors.forename: A F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: J D
authors.initials: JD
authors.lastname: Minna
mesh_terms: D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000556:secondary; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011544:Pseudogenes; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human