Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer.
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.
Mousses
S
S
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Ozçelik
H
H
Lee
P D
PD
Malkin
D
D
Bull
S B
SB
Andrulis
I L
IL
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
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers