Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer

Hum Mol Genet. 1995 Jun;4(6):1089-92. doi: 10.1093/hmg/4.6.1089.


Several groups have recently isolated and characterized an inhibitor of cyclin-dependent kinases, p21CIP1/WAF1 which is transcriptionally induced by wild-type but not mutant p53. It is likely that p21CIP1/WAF1 mediates the growth suppression effects of p53 by arresting the cell cycle at the G1/S checkpoint, and by inducing apoptosis. To test the hypothesis that primary human tumors have mutations in the CIP1/WAF1 gene which propagates the carcinogenic process, we examined primary breast and sarcoma tumor specimens for alterations in the CIP1/WAF1 gene. Unique, or acquired somatic mutations were not observed indicating that they are not selected for during the carcinogenic process; however, two common variants were identified. The variants were not unique to tumors as 10.7% of normal individuals exhibited the variants. Nonetheless, the frequency of the variants in tumors with wild-type p53 (20.4%) was significantly greater (p = 0.05) than in normal DNAs. In contrast, the frequency of the variants (4.1%) was found to be significantly lower in tumors with p53 mutations (p = 0.006). These data suggest that the occurrence of the variants may have a direct effect on tumor development and may, in some cases, be incompatible with p53 mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Chromosomes, Human, Pair 6
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics*
  • DNA Primers
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Neuroblastoma / genetics
  • Polymerase Chain Reaction
  • Rhabdomyosarcoma / genetics
  • Sarcoma / genetics*
  • Sarcoma / pathology


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA Primers

Associated data

  • GENBANK/L47232
  • GENBANK/L47233