title: Mutations and deletions of the CBP gene in human lung cancer.
abstract: OBJECTIVE
  Microarray-based comparative genomic hybridization analysis led us to detect a homozygous deletion at the cyclic AMP response element binding protein-binding protein (CBP) locus in a lung cancer cell line. Oncogenic roles of CBP had been suggested by functional and genetic studies; thus, involvement of CBP gene alterations in lung carcinogenesis was investigated by undertaking comprehensive analysis of genetic CBP alterations in human lung cancer.
  
  
  METHODS
  Fifty-nine cell lines and 95 surgical specimens of lung cancer were analyzed for mutations, homozygous and hemizygous deletions, and expression of the CBP gene.
  
  
  RESULTS
  Homozygous CBP deletions, including two intragenic deletions, were detected in three (5.1%) lung cancer cell lines. CBP mutations, including missense, nonsense, and frame-shift mutations, were detected in six (10.2 %) cell lines and five (5.3%) surgical specimens of lung cancer. The wild-type CBP allele was retained in 9 of 11 cases with CBP mutations, and both the wild-type and mutant alleles were expressed in all the six cases with heterozygous CBP mutations examined. Three mutations with amino acid substitutions in the histone acetyltransferase domain caused significant reduction in transcription activation activity of CBP protein in vivo.
  
  
  CONCLUSIONS
  A fraction of lung cancers carried mutations and/or deletions of the CBP gene, suggesting that genetic CBP alterations are involved in the genesis and/or progression of a subset of lung cancers.
authors.affiliation: Biology Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-Chome Chuo-Ku, Tokyo 104-0045, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kishimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Koji
authors.initials: K
authors.lastname: Okudela
authors.forename: Ayaka
authors.initials: A
authors.lastname: Otsuka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Chikako
authors.initials: C
authors.lastname: Tanabe
authors.forename: Tokuki
authors.initials: T
authors.lastname: Sakiyama
authors.forename: Chie
authors.initials: C
authors.lastname: Hirama
authors.forename: Issay
authors.initials: I
authors.lastname: Kitabayashi
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein; D004273:DNA, Neoplasm / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D004273:DNA, Neoplasm; D014157:Transcription Factors; D000123:Acetyltransferases