title: Detection of point mutations in promoter and coding sequence of p21 gene in a variety of human malignancies.
abstract: OBJECTIVE
  p21 is a general inhibitor of cyclin-dependent kinases which leads cells through restriction point of cell cycle. Since p21 has been identified to be a mediator of p53 tumor suppressor activity and directly up-regulated by p53, this study was designed to investigate whether mutations in promoter or coding sequence of p21 were associated with development or progress of tumor.
  
  
  METHODS
  A 2.4kb DNA fragment, containing essential promoter, was amplified and sequenced. Furthermore, 346 DNA samples from 9 different types of primary tumors were examined for point mutations in promoter and coding sequence of p21 gene by using SSCP analysis and direct sequencing.
  
  
  RESULTS
  Heterozygous or homozygous G to A transition at 5bp upstream and C to A transversion at 160bp downstream of p53 binding site were found. A 44bp heterozygous deletion was detected in a bladder cancer, which started at codon 34 and resulted in frameshift and a premature stop codon downstream. The most abundant variants in coding sequence of p21 gene were a C to A transversion at codon 31 which resulted in Ser to Arg and had been identified being polymorphism. In addition, four rare variants in coding sequence were also found.
  
  
  CONCLUSIONS
  The evidence from this study indicates that mutation in either promoter or coding sequence of p21 gene is rare in a variety of human malignancies.
authors.affiliation: Central Laboratory, the First People's Hospital, Shanghai, 200080 P. R. China. huangq@online.sh.cn
authors.forename: Q
authors.initials: Q
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Tao
mesh_terms: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D017354:Point Mutation; D011401:Promoter Regions, Genetic
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins