title: Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer.
abstract: 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.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Mousses
authors.forename: H
authors.initials: H
authors.lastname: Ozçelik
authors.forename: P D
authors.initials: PD
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Malkin
authors.forename: S B
authors.initials: SB
authors.lastname: Bull
authors.forename: I L
authors.initials: IL
authors.lastname: Andrulis
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002896:Chromosomes, Human, Pair 6; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D017931:DNA Primers; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics; D016133:Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000235:genetics; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers