NO POINT MUTATIONS BUT A CODON-31 POLYMORPHISM AND DECREASED EXPRESSION OF THE P21(SDI1 WAF1/CIP1/MDA6) GENE IN HUMAN GASTRIC CARCINOMAS/

p21(SDI1), also known as WAF1/CIP1/MDA6, is a potent inhibitor of cycl in-dependent kinases, which is transcriptionally induced by wild-type p53 but not by mutant p53. Genetic status and expression of p21 was ex amined in human gastric carcinoma cell lines as well as carcinoma tiss ues. Three our of eight gastric carcinoma cell lines showed a single n ucleotide substitution at codon 31 that changes from AGC to AGA (Ser t o Arg). This change at codon 31 was also detected in both surgically r esected primary gastric carcinoma tissues and their corresponding norm al mucosas, indicating a polymorphism of the p21 gene. Northern blot a nalysis revealed a decreased expression of p21 in 8 of 15 (53%) gastri c carcinoma tissues when compared with their corresponding normal muco sas, although no obvious correlation was observed between the expressi on of p21 mRNA and the polymorphism at codon 31. Half of the gastric c arcinoma cases showed an inverse correlation between the expression of the p21 and p53 genes. These findings suggest that (1) a polymorphism of the p21 gene might not participate in altered expression of p21 in gastric carcinomas, and (2) p53-independent pathway might be consider ably involved in the induction of p21 in gastric carcinomas.