title: Homozygous deletions of the INK4a/ARF locus in renal cell cancer.
abstract: BACKGROUND
  Genetic alterations of p14ARF contribute to dysfunction of p53 pathways by disruption of MDM2-mediated inhibition of p53. P14(ARF) was investigated by focusing on the homozygous deletion (HD) in the INK4a/ARF locus and hypermethylation of the p14(ARF) promoter in renal cell cancer (RCC).
  
  
  METHODS
  Using 6 RCC cell lines, RT-PCR and Western blotting was performed for p14(ARF). DNA from 34 RCCs was analyzed for HD in the INK4a/ARF locus, promoter hypermethylation and p53 gene mutation.
  
  
  RESULTS
  HD was confirmed in 4 out of 6 cell lines and in 8 out of 34 (23.5%) RCC specimens, which correlated with the presence of metastasis, high tumor grade and had a tendency to more advanced stage (I vs. II-IV). No hypermethylation of the p14(ARF) promoter or p53 mutation was detected among the RCC specimens.
  
  
  CONCLUSIONS
  These results indicate that the deletion in the INK4a/ARF locus might contribute to tumor progression in RCC at least partly by functional inactivation of wild-type p53.
authors.affiliation: Division of Molecular Oncology, Niigata University Grauate School of Medical and Dental Sciences, Asahimachi 1-757, Niigata, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kasahara
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bilim
authors.forename: Noboru
authors.initials: N
authors.lastname: Hara
authors.forename: Kota
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tomita
mesh_terms: D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers