A MUTANT P21 CYCLIN-DEPENDENT KINASE INHIBITOR ISOLATED FROM A BURKITTS-LYMPHOMA

The growth arrest mediated by p53 is caused at least in part by the p5 3 mediated expression of p21 (p21(waf1/Cip1)). Since only one-third of primary Burkitt's lymphomas (BL) demonstrate mutations in the p53 gen e, we examined the structural integrity of the p21 coding region by si ngle-strand conformational polymorphism and DNA sequence analysis to d etermine the extent to which this gene is mutated in BL. Of 34 BLs ana lyzed, a frequent change (38%) at codon 31 that replaced Ser with Arg was found in 13 samples, 10 of which were from Africa. This change at codon 31 is also detected in peripheral blood DNA from normal subjects and may thus represent a polymorphism. One BL cell line, DH978, carri ed a change at codon 63: Phe to Leu. This mutation was heterozygous, a nd both the wild-type and the mutated p21 mRNA were expressed in the t umor cell Line. By transfection experiments, the mutant p21 was less e fficient in suppressing clonogenicity than wild-type p21. To our knowl edge, this is the only mutation described in p21. The availability of this mutant p21 should further help in functional studies of p21.